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Publication numberUS20040242953 A1
Publication typeApplication
Application numberUS 10/652,231
Publication dateDec 2, 2004
Filing dateAug 29, 2003
Priority dateAug 13, 1990
Also published asCA2067804A1, DE69130944D1, DE69130944T2, EP0500928A1, EP0500928A4, EP0500928B1, US6099457, US6666811, WO1992003179A1
Publication number10652231, 652231, US 2004/0242953 A1, US 2004/242953 A1, US 20040242953 A1, US 20040242953A1, US 2004242953 A1, US 2004242953A1, US-A1-20040242953, US-A1-2004242953, US2004/0242953A1, US2004/242953A1, US20040242953 A1, US20040242953A1, US2004242953 A1, US2004242953A1
InventorsRoger Good
Original AssigneeEndotech, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Endocurietherapy
US 20040242953 A1
Abstract
To provide versatile radioactive implants and methods of radiation therapy, plating methods such sputtering, as are used to coat single elements such as microspheres, wires and ribbons with radioactive metals, protective layers and identification layers. The resulting solid, radioactive, multilayered seamless elements are implanted individually or combined in intercavity applicators, with fabrics and in ribbons. Because they have selected half-lives and intensities, they provide flexibility in treatment, permitting low intensity or high intensity treatment using temporary or permanent implants and implants with high intensity or low intensity or contoured intensity to permit different therapies.
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Claims(26)
What is claimed is:
1. A method of forming a one-piece substantially spherical seamless multilayered radioactive seed, comprising the steps of:
forming a central sphere having an outer diameter less than 1 millimeter;
forming a layer section over said central sphere with no substantial voids between the central sphere and the layer section having an outside diameter larger than said central sphere but less than 1 millimeter, wherein said layer section includes at least an outer layer of non-radioactive material concentric with the central sphere; and
including within said outer layer a therapeutic amount of radioactivity with a diffusion barrier separating said therapeutic amount of radioactivity and the outside surface of said outer layer, wherein said one-piece substantially spherical seamless multilayered radioactive seed may be directly implanted in contact with a patients tissue.
2. A method in accordance with claim 1 in which the step of forming a layer section includes the step of forming an optional special purpose spherical coat designed to enhance diagnostic imaging.
3. A method in accordance with claim 1 in which the step of forming a layer section includes the step of forming a spherical coat including a radionuclide with a weighted average gamma energy of less than 100 KeV, and with a half-life of less than 130 days, wherein a multilayer radioactive microsphere is a low energy permanent multilayered radioactive microsphere for permanent interstitial implantation into human tumor tissues.
4. A method in accordance with claim 1 in which the step of forming a layer section includes the step of forming a spherical coat including a radionuclide with a weighted average gamma energy of less than 100 KeV and with a half-life of less than 130 days, wherein the one-piece substantially spherical seamless multilayered radioactive seed is a high energy permanent multilayered radioactive microsphere for permanent interstitial implantation into human tumor tissues.
5. A method in accordance with claim 1 in which the step of forming a layer section includes the step of forming a spherical coat including a radionuclide with a weighted average gamma energy greater than or equal to 100 KeV and with a half-life of less than 15 to 20 days, wherein the one-piece substantially spherical seamless multilayered radioactive seed is a high energy permanent multilayered radioactive microsphere for permanent interstitial implanatation into human tumor tissues.
6. A method in accordance with claim 1 in which the step of forming a layer section includes the step of forming a spherical coat including a radionuclide with a weighted average gamma energy of less than 100 KeV and with a half-life greater than 130 days, wherein the one-piece substantially spherical seamless multilayered radioactive seed is a high energy permanent multilayered radioactive microsphere for permanent interstitial implantation into human tumor tissues.
7. A method in accordance with claim 1 in which the step of forming a layer section includes the step of forming at least one spherical coat by inserting the central sphere with a substrate to be coated exposed into a vacuum chamber;
levitating the central sphere with the substrate to be coated; and
applying material under vacuum to the substrate while the substrates are levitated.
8. A method in accordance with claim 7 in which the step of forming a layer section further includes the step of applying a bias to avoid fusing the substrates to the levitating means.
9. A method in accordance with claim 7 in which the step of levitating the central sphere includes the step of applying ultrasonic vibrations to the central spheres.
10. A method in accordance with claim 9 in which the step of applying ultrasonic vibrations includes the step of applying ultrasonic vibrations at a frequency between 1 and 10 percent of the levitating means resonant frequency.
11. A method in accordance with claim 1 in which the step of forming a layer section further includes the step of forming a layer of a ferromagnetic alloy that is capable of being inductively heated in situ by applied radiofrequency radiation until it passes through a Curie transition at temperatures useful for clinical hyperthermia.
12. A method in accordance with claim 1 in which the step of forming a layer section further includes the step of dc sputtering material using a radioactive metal target.
13. A method in accordance with claim 1 in which the step of forming a layer section further includes the step of rf or magnetron sputtering using a radioactive dielectric target.
14. A method in accordance with claim 1 in which the step of forming a layer section further includes the step of a metal in the presence of a gaseous radionuclide such as a radioactive hydride gas or monoatomic gas wherein a radioactive metal compound coat is formed as the coat by combining the metal with the radioactive component of the gas.
15. A method in accordance with claim 1 in which the step of forming a layer section further includes the step of dc sputtering material using a radioactive metal target wherein a dielectric coated planar metal target is prepared by coating a metal planar substrate with a radioactive dielectric compound using a selected one of reactive dc, rf, and magnetron sputtering, reactive cathodic arc plasma deposition, reactive ion-beam sputtering and reactive ion plating in which the radioactive compound coat is produced from an excited radionuclide gas and a non-radioactive metal target, whereby a target may be prepared for any one of cathodic arc plasma deposition or, rf or magnetron sputtering, or ion plating, or ion beam sputtering.
16. A method in accordance with claim 1 in which the step of forming a layer section further includes the step of laminating coats of low boiling point elements that are likely to vacuum weld with high boiling point elements that are unlikely to vacuum weld.
17. An auto-feeding implantation gun for implantation of multiple multilayer radioactive microspheres comprising:
a loading chamber having in inner diameter of less than 1 millimeter and a length of at least 10 millimeters; and
means for ejecting radioactive spheres having diameters less than 1 millimeter, said means for ejecting radioactive spheres including at least one spring biased container for spheres and pin means for holding the spheres from ejection.
18. A method for eliminating vacuum welding between levitated microspheres comprising the steps of:
laminating coats of low boiling point elements that are likely to vacuum weld with high boiling point elements that are unlikely to vacuum weld; and
biasing a levitating bouncing pan with an electric charge.
19. A method of depositing radioactive material onto a substrate wire to form a multilayered seamless radioactive wire in such a manner that a therapeutic amount of radio activities are deposited in a controlled fashion comprising the steps of:
coating a central wire section with a plurality of coats to form a layer section wherein at least one layer has a therapeutic amount of radioactivity and there is an outside diameter no greater than 1 millimeter;
at least certain of said coats are applied to said wire substrate by one of sputtering, laser ablation deposition, ion plating, ion beam sputtering, or cathodic arc deposition and are spattered from a material that reacts chemically with the radioactive material and forms a mechanical barrier against diffusion of the radioactive material.
20. A method of depositing radioactive material onto a substrate wire to form a multilayered seamless radioactive wire in such a manner that a theraputic amount of radioactivities are deposited in a controlled fashion comprising the steps of:
differentially coating radioactive material onto said substrate wire to form a multilayered seamless radioactive wire in such a manner that variable activities are deposited per unit length in a controlled fashion;
at least certain coats of said multilayered wire being applied to said wire substrate by one of sputtering, laser ablation deposition, ion plating, ion beam sputtering, or cathodic arc deposition and are spattered from a material that reacts chemically with the radioactive material and forms a mechanical barrier against diffusion of the radioactive material.
21. A method of making an ocular applicator comprising the steps of coating a substrate with a material containing a therapeutic amount of radioactivity and a protective layer wherein radioactive multilayers in the layer section have a thickness no greater than 0.5 millimeters and are deposited on an active surface by means of sputtering, laser ablation deposition, ion plating, ion beam sputtering, or cathodic arc deposition and are spattered from a material that reacts chemically with the radioactive material and forms a mechanical barrier against diffusion of the radioactive material.
22. A surgical technique for implantation of multilayer radioactive microspheres the steps of:
selecting the half-life, energy, activity and field strength of the implant in accordance with the time of implantation; and
implanting high energy microspheres wherein the high energy microspheres include high energy radioactivity with a half-life only long enough to destroy only neoplantic tissue and not long enough for the destruction of differentiated healthy cells according with the intensity, and low energy radioactivity with a long half-life.
23. A surgical technique for implantation of ribbon-multilayer radioactive implants comprising the steps of:
selecting a ribbon with the intensity, activity, energy and spacing of radioactive seeds appropriate for the tumor size and type;
inserting the ribbon in a path covering the diseased tissue using a needle, catheter, tube, or cartridge-fed implantation gun, the step of inserting including the step of anchoring the ribbon by inserting beads connected thereto into said tissue.
24. A surgical technique for temporary implantation of multilayered radioactive wire comprising the steps of:
selecting a wire with the intensity, activity, and energy appropriate for the tumor size and type; and
inserting the wire or multiple wires in a path covering the diseased tissue, and removing the wires after a therapeutic amount of time, the step of inserting including the step of anchoring the wire by inserting beads connected thereto into tissue.
25. Apparatus for coating small substrates comprising:
a vacuum chamber;
substrate levitating means for levitating substrates to be coated;
means for applying material under vacuum to the substrates while the substrates are levitated; and
means for applying a bias to avoid levitating means.
26. Apparatus for coating small substrates comprising:
a vacuum chamber;
substrate levitating means for levitating substrates to be coated;
means for applying material under vacuum to the substrates while the substrates are levitated;
said levitating means including an ultrasonic vibrator and means for driving the ultrasonic vibrator at a frequency between 1 and 10 percent of levitating means resonant frequency.
Description
    REFERENCE TO RELATED APPLICATIONS
  • [0001]
    This application is a divisional of parent application Ser. No. 09/633,437 filed Aug. 7, 2000, which is a divisional of parent application Ser. No. 07/741,038 filed Aug. 6, 1991, now U.S. Pat. No. 6,099,457, which is a continuation-in-part application of U.S. application Ser. No. 07/565,714 for ENDOCURIETHERAPY filed by Roger R. Good on Aug. 13, 1990, now U.S. Pat. No. 5,342,283.
  • BACKGROUND OF THE INVENTION
  • [0002]
    This invention relates to radioactive implants, methods of making them and methods of using them.
  • [0003]
    It is known to use external beam supervoltage or megavoltage conventional fractionated radiation therapy to treat subclinical microscopic metastases in surgically undisturbed lymph node chains and to sterilize the postoperative tumor bed after the tumor is grossly excised. The uses of external beam radiation techniques have a disadvantage that they are not able to safely treat solid tumors because the solid tumors require an intensity of radiation that is harmful to the surrounding normal tissue.
  • [0004]
    It is also known to implant radioactive sources directly into solid tumors for the destruction of the tumors in a therapy referred to as brachytherapy (short-range therapy). This therapy permits the application of larger doses of radiation.
  • [0005]
    In the prior art brachytherapy, the sources are generally implanted for short periods of time and generally are sources of high radiation intensity. For example, radium needles and iridium-192 ribbons have been implanted into tumors (interstitial brachytherapy) or radium-226 capsules and cesium-137 capsules have been placed into body cavities such as the uterus (intracavitary brachytherapy).
  • [0006]
    The prior art interstitial brachytherapy treatment using radium needles has several disadvantages, such as for example: (1) dosimetry is difficult and imprecise; (2) local failures are caused, mainly by the large size of the radium needles (approximately the size of a lumber nail); (3) it is difficult to implant an adequate number of the needles uniformly throughout a tumor to produce homogeneous irradiation because they are large sources; and (4) the needles can only be left in place temporarily, and must be surgically removed.
  • [0007]
    It is known to implant iodine seeds temporarily or permanently. The prior art iodine seed consists of the radionuclide adsorbed onto a carrier which is placed into a metal tube that is welded shut. It has the disadvantages of: (1) being relatively large to be safely implanted in large numbers in the human body; and (2) due to its construction, producing inhomogeneous radiation.
  • [0008]
    The prior art iridium seeds in ribbon consist of solid iridium wire cut into pieces and placed in plastic tubing, which is then implanted into accessible tissues temporarily for several days. These seeds work well, but because they must be removed, their application is limited to a few accessible body sites. Also, they only come in one energy.
  • [0009]
    The prior art radium-226 intracavitary sources and cesium sources consist of metal cylinders containing radium salts or cesium. They have several disadvantages, such as for example: (1) dosimetry is difficult and imprecise; (2) they are bulky and difficult to use; (3) it is difficult to implant or otherwise insert an adequate number of the cylinders in the proper locations to produce homogeneous irradiation because they are large sources; (4) the cylinders can only be left in place temporarily, and under some circumstances, must be surgically removed; and (5) general anesthesia is required to dilate the cervix sufficiently to place a source in the uterus.
  • [0010]
    The applications of brachytherapy are still severely limited by the unavailability of a wide range of implantable radioactive sources that have a wide range of gamma energies (radiation energy is related to the volume irradiated) and varying half-lives (radionuclide half-life affects tumor dose rate, radiobiology, and normal tissue effects). Also the limited number of sources currently available are still physically unsatisfactory in their construction. There are few low energy limited lifetime radioactive seeds such as gold-198 and iodine-125 seeds that may be permanently implanted into solid cancers.
  • [0011]
    It is also known to apply heat to tumors by implanting metals that may be heated by radio frequency radiation and to move heatable or radioactive members about magnetically for positioning them without excessive surgery. This is especially significant in the treatment of highly vascular tumors. The existing hyperthermia radio frequency treatment is not well adapted for easy combination with endocurietherapy.
  • SUMMARY OF THE INVENTION
  • [0012]
    Accordingly, it is an object of the invention to provide novel radioactive implants.
  • [0013]
    It is a still further object of the invention to provide a novel electron-producing beta-seed.
  • [0014]
    It is a still further object of the invention to provide a perfectly spherical tantalum, tungsten, gold, platinum casing or compound tungsten carbide, tantalum carbide casing over a radioactive microspherical substrate when the radioactive material produces high energy gamma rays.
  • [0015]
    It is a still further object of the invention to provide a perfectly spherical titanium, hafnium or zirconium metal casing or a compound casing of titanium carbide, titanium nitride, titanium conbonitride, hafnium nitride or zirconium nitride over a radioactive microspherical substrate when the radioactive material produces low energy gamma rays.
  • [0016]
    It is a still further object of the invention to provide a perfectly spherical diamond casing over a radioactive microsphere when the radioactive material produces beta rays.
  • [0017]
    It is still further object of the invention to produce a novel low-energy permanent multilayered radioactive microsphere.
  • [0018]
    It is a still further object of the invention to provide a novel tissue-compatible (absorbable and non-absorbable) surgical fabric that contains multiple radioactive seeds to facilitate rapid implantation of a large number of radioactive seeds.
  • [0019]
    It is a still further object of the invention to provide a novel ribbon containing multiple low energy permanent multilayered radioactive microspheres.
  • [0020]
    It is a still further object of the invention to provide a novel multilayered low energy permanent or temporary radioactive wire that may be permanently or temporarily implanted into human tissues and that safely delivers low energy.
  • [0021]
    It is a still further object of the invention to provide a novel implant that safely delivers energy at levels less than or equal to 100 KeV average gamma energy to tumors at a low rate in less than 130 days to produce tumoricidal radiation doses that are 2.3 to 5.7 times higher than the maximum doses permissible with reasonable safety by modern megavoltage external beam radiation therapy techniques.
  • [0022]
    It is a still further object of this invention to produce a radioactive seed which has the clinical result of reducing the complication rate of treatment while increasing the local cure rate by allowing safe delivery of very high radiation doses to solid human tumors.
  • [0023]
    It is still further object of the invention to produce an improved radioactive seed, ribbon containing multiple seeds, or radioactive wire which may be permanently implanted into human tissues and safely deliver high energy (greater than 100 KeV average gamma energy) tumor irradiation at an average dose rate less than 1.50 Gy/hour (Gray/hour-one Gray is equal to 100 rad) in less than 15 to 20 days.
  • [0024]
    It is a still further object of the invention to provide a novel technique for making an improved radioactive seed, seed ribbon, or radioactive wire which may be temporarily implanted into human tissues by after-loading tubes or by implanting interstial needles.
  • [0025]
    It is a still further object of the invention to produce a novel multilayered radioactive microsphere, ribbon microsphere, or multilayered radioactive wire, which emits electrons or beta particles and have casings which are substantially transparent to electrons.
  • [0026]
    It is a still further object of the invention to provide a radioactive seed having a shape that is spherical rather than cylindrical to make it less likely to jam in an auto-feeding tissue implantation gun.
  • [0027]
    It is a still further object of the invention to increase the clinical utility and safety of the radioactive seed by making it significantly smaller in diameter to permit tissue implantation with thinner gauge needles.
  • [0028]
    It is a still further object of the invention to improve upon the uniformity of the radioactive coat used in radioactive seed production.
  • [0029]
    It is a still further object of the invention to produce a radioactive seed which contains multiple coats which have specialized purposes.
  • [0030]
    It is a still further object of the invention to produce a radioactive seed which contains a diffusion barrier coat over the radionuclide layer.
  • [0031]
    It is a still further object of the invention to produce a radioactive seed which contains a coat that enables visualization of the seed in tissue such as by magnetic resonance imaging (NMR, MR) or X-ray or single positron resonance (SPECT) or positron emitting tomography (PET) or the like.
  • [0032]
    It is a still further object of the invention to produce radioactive seeds that contain different magnetic resonance imaging marker coat to enable separate individual identification of one type of seed from another type of seed when seeds containing different radionuclides are implanted into the same tumor.
  • [0033]
    It is a still further object of the invention to produce an outermost seed coat which reduces friction, adds coloring for seed type identification, increases hardness and durability, and increases tissue compatibility and corrosion resistance.
  • [0034]
    It is a still further object of the invention to produce a more miniaturized intracavitary source that may be placed into the uterus without endocervical dilation or into the bladder with minimal trauma to the urethra and is available in a wide range of energies and isotopes.
  • [0035]
    It is a still further object of the invention to provide a radioactive seed that can be raised to a selected temperature by remotely radiated energy for hyperthermia.
  • [0036]
    It is a still further object of the invention to provide a radioactive seed that can be moved by remotely originated radiant energy.
  • [0037]
    It is a further object of the invention to provide novel techniques for manufacturing radioactive implants.
  • [0038]
    It is a still further object of the invention to provide techniques for manufacture of radioactive seeds containing a wide variety of radionuclides with different energies and half-lives.
  • [0039]
    It is a still further object of the invention to provide techniques for manufacturing a wide variety of radio-nuclides including those useful for permanent implantation into human tissues, those useful for temporary removable interstitial needle or ribbon implantation into human tissues, and those useful for temporary intracavitary irradiation.
  • [0040]
    It is a, still further object of the invention to mass manufacture microspherical seeds less than 0.40 millimeter in diameter that may contain a therapeutic amount of radioactivity, a hard tissue-compatible protective coat, and several special purpose coats.
  • [0041]
    It is a still further object of the invention to provide a novel technique for manufacture of multiple radioactive seeds connected by a ribbon or wire to facilitate rapid implantation of multiple seeds.
  • [0042]
    It is still further object of the invention to provide a novel technique for manufacture of multilayered radioactive wires that contain a wide variety of different radionuclides for use in temporary removable tumor implants.
  • [0043]
    It is a still further object of the invention to manufacture a novel small-diameter (less than one millimeter) high-activity intracavitary source using any of a variety of different radionuclides.
  • [0044]
    It is a still further object of the invention to present a novel method for incorporation of a radionuclide into a seed during manufacture of the seed.
  • [0045]
    It is a still further object of the invention to provide a novel method for incorporation of a non-radioactive elemental isotope into a seed during manufacture of a seed that will later form the desired radioactive isotope when the finished seed is bombarded with neutrons.
  • [0046]
    It is a still further object of the invention to provide a method for making a perfectly spherical titanium casing over a radioactive microspherical substrate when the radioactive material produces low energy gamma rays.
  • [0047]
    It is a still further object of the invention to provide a less expensive seed by eliminating the need for human or mechanical assembly of separate parts and welding of individual seeds.
  • [0048]
    It is a still further object of the invention to provide an effective low cost method for large-scale mass-manufacture of high quality radioactive seeds for use in implantation of human tissues and to make the seeds readily available for use in large numbers of patients on a daily basis.
  • [0049]
    It is still further object of the invention to provide means of modified manufacturing processes which allows great versatility in manufacturing seeds of a variety of designs containing different combinations of types of radionuclides, metal and alloy coats, and elemental nonmetallic as well as compound hard coats.
  • [0050]
    It is a still further object of the invention to introduce a versatility of manufacturing process that permit manufacture of improved seeds which have varied physical characteristics including different average gamma radiation energies and different average lifetimes.
  • [0051]
    It is a still further object of the invention to provide a combination of manufacturing techniques that permit optimally matched seeds for the physical location and radiobiology of the tumor type or cancerous tissue they are designed to destroy.
  • [0052]
    It is a still further object of the invention to provide novel method for production of radioactive microspheres, ribbon microspheres or wires in which the radioactive component is incorporated into the microsphere by the reaction of an excited radionuclide gas with a target material produced by reactive coating techniques.
  • [0053]
    It is a still further object of the invention to provide a novel method for production of radioactive microspheres, ribbon microspheres, or wires in which the radioactive component is incorporated into the microsphere by sputtering, laser ablation, cathodic arc plasma deposition or curvilinear cathodic arc plasma deposition from a target material consisting of a radioactive dielectric compound material or a radioactive metal.
  • [0054]
    It is a still further object of the invention to provide novel techniques for using radioactive implants.
  • [0055]
    It is a still further object of the invention to provide a novel technique for eliminating the radiation dose anisotropy problems characteristic of the tungsten end-welded cylindrical radioactive seeds.
  • [0056]
    It is a still further object of the invention to reduce the danger of radioactive contamination of the hospital environment.
  • [0057]
    It is a still further object of the invention to reduce the danger of case rupture of the radioactive seed by eliminating the free space between the radioactive component and the casing.
  • [0058]
    It is a still further object of the invention to reduce the danger of radiation exposure to personnel involved in seed assembly.
  • [0059]
    A still further object of the invention is to produce a radioactive seed which has the clinical result of reducing the complication rate of treatment while increasing the local cure rate by allowing safe delivery of very high radiation doses to solid human tumors.
  • [0060]
    It is a still further object of the invention to provide a novel therapy for necrosis of tumors.
  • [0061]
    It is a still further object of the invention to provide a novel therapy which combines low dose continuous radiation with higher dosage radiation for the destruction of tumors.
  • [0062]
    It is a still further object of the invention to provide a novel therapy for the incorporation of low energy implants into a tumor with externally applied high energy treatment to destroy a tumor.
  • [0063]
    It is a still further object of the invention to provide a novel therapy in which cancer cells are biased toward a sensitive state and then irradiated for a short period of time while in the sensitive state.
  • [0064]
    It is a still further object of the invention to produce a radioactive seed which has the clinical result of serving as a radiation sensitizer when implanted prior to administration of conventional external-beam radiation therapy and which delivers continuous low dose rate radiation to block tumor cells in the most radiation sensitive portions of their cell cycle.
  • [0065]
    According to the above and further objects of the invention, a one-piece solid spherical seamless multilayered radioactive seed, herein sometimes referred to as a multilayered radioactive microsphere includes a spherical radioactive thin layer with a therapeutic amount of activity. The spherical seed has several desirable characteristics such as for example: (1) its contents may provide up to 1000 millicuries of activity and a completely spherical photon fluence without significant anisotropy; and (2) there is no free space between the radioactive component and the casing.
  • [0066]
    In a preferred embodiment, it includes a microspherical central marker, a spherical radioactive thin coat containing a therapeutic amount of activity, a spherical diffusion barrier coat, an optional special purpose spherical coating designed to enhance diagnositc imaging, a thick spherical (up to 0.10 mm) protective coating containing the inner coats, and an optional thin outermost special-purpose coat in the order listed. The multilayered radioactive microsphere contains: (1) no free spaces or cavities; and (2) no end-welds. The central marker or special coat for imaging may be selected for X-ray, PET, SPECT or MR or any other type of imaging.
  • [0067]
    The multilayer radioactive micropsphere radionuclide is selected for the desired purpose. For example, for a first group of purposes, the radionuclide has a weighted average gamma energy of less than 100 KeV, with a half-life of less than 130 days. This multilayer radioactive micropsphere is referred to as a low energy permanent multilayered radioactive microsphere for permanent interstitial implantation into human tumor tissues. The corresponding multilayer radioactive microsphere with a gamma energy greater than 100 KeV is referred to as a high energy permanent multilayered radioactive microsphere for permanent interstitial implantation into human tumor tissues. Preferably, its half life is less than 15 to 20 days.
  • [0068]
    For a second group of purposes, the radionuclide has a weighted average gamma energy greater than or equal to 100 KeV, with a half-life of greater than 15 to 20 days, or an average energy less than 100 KeV and a half-life of greater than 130 days. This multilayered radioactive microsphere is referred to as a temporary removable multilayered radioactive microsphere for temporary removable interstitial implantation into human tumor tissues.
  • [0069]
    For a third group of purposes, the radionuclide emits a high energy electron particle without significant high-energy gamma-ray component. This multilayer radioactive microsphere is referred to as an electron-producing or beta multilayered radioactive microsphere for permanent or temporary removable interstitial implantation into human tumor tissues.
  • [0070]
    The shape, size and packaging of the multilayered radioactive seeds are appropriate for their purposes, such as being a microsphere having a diameter of 0.40 millimeters or less for use in injection equipment or in the case of wire or ribbon, having a similar diameter to permit interstitial tissue implanation through a regular 21 gauge needle or through a thin-walled 22 gauge needle.
  • [0071]
    The radioactive coat of the multilayered radioactive microsphere comprises one or more of: (1) a metal such as palladium-103, gold-198, thulium-170, or chromium-56, a mixture of metals, a mixture of compounds including radioactive metals or radionuclides, or a radionuclide bound to a metal; or (2) a dielectric radioactive element such as arsenic-73, yttrium-90, or iodine-125 or compound dielectric materials containing one non-radioactive and one radioactive component such as zirconium iodide Zr(I-125)4, hafnium iodide Hf(I-125)4, titanium iodide Ti(I-125)2, silveriodide-125, thulium bromide-170, magnesium arsenide-73, potassium iodide-125, rubidium silver iodine-125, or copper iodide-125; or (3) any combination of radioactive dielectric compounds; or (4) two or more radioactive components, such as for example arsenic-73 and di-iodide-125, arsenic-73, selenide-75, or palladium-103 and iodide-125.
  • [0072]
    The radioactive coat may also be formed in different configurations such as by being laminated together with a non-radioactive high boiling point or hard metal by sputtering, laser ablation ion plating, ion beam sputtering, or cathodic arc deposition; (2) by being uniformly covered by a spherical diffusion barrier that may consist of a coat of single metals such as gold, tantalum, palladium, and titanium or several layers of metals or compounds such as titanium-palladium-gold, gold-titanium, titanium nitride (TiN), zirconium nitride (ZrN), titanium carbide (TiC), titanium (T), tungsten/titanium (W/T), tungsten carbide (WC), tungsten nitride (WN), tungsten/titanium nitride (WTN), hafnium nitride (HfN), Hafnium carbide (HfC), zirconium carbide (ZRC), Vanadium carbide (VC), boron carbide (BC), tungsten boride (WB) or diamond. The diffusion barrier may be covered by a uniform spherical thick (up to 0.10 millimeter) protective coat.
  • [0073]
    Either inside the radioactive layer or over the diffusion barrier inside the protective coat, there may be an inner spherical uniform special purpose coat. This special purpose coat may be used to enhance imaging of the multilayer radioactive microsphere by means of conventional radiographs or MR, CT, SPEC or PET imaging. For example, the special spherical inner coat may consist of gadolinium for magnetic resonance imaging of the multilayer radioactive microsphere.
  • [0074]
    The spherical thick outside protective coat may be composed of: (1) a resistant human tissue-compatible metal which also has low atomic weight to minimize X-ray shielding such as titanium or other corrosion-resistant metal alloy such as stainless steel; or (2) a resistant human tissue-compatible metal compound (using reactive nitrogen, oxygen, methane, or carbon monoxide gases during coating to form carbides, nitrides, or carbonitrides of transition metals or other metals) such as titanium carbide, titanium nitride, titanium carbonitride, titanium aluminum nitride, zirconium nitride and hafnium nitride; or (3) a resistant human tissue-compatible metal coating less than 0.1 millimeters thick which has a high atomic weight such as tantalum, platinum or gold or the corresponding compounds of tungsten carbide, tantalum carbide, or platinum oxide; or (4) a human tissue-incompatible metal coating which is covered by a tissue-compatible thin coating.
  • [0075]
    If a tissue-compatible outermost thin coat is included it may be sputtered diamond, tantalum, tungsten or titanium and should overlay the thick protective metal casing. In this case, the more toxic but low atomic weight metals such as beryllium, vanadium, nickel and boron nitride may be used as the thick protective casing. The thin outer coats may consist of a special-purpose coats designed to enhance physical properties of the seed such as diamond or diamond-like carbon, platinum, or tantalum. These coats individually enhance the multilayer radioactive microsphere by adding hardness, and corrosion resistance.
  • [0076]
    The outermost thin coat may also be used to produce different seed identification colors. For example, the outermost thin coat may consist of titanium nitride (TiN) to produce a golden color, titanium carbonitride (TiCN) to produce a brown color, titanium aluminum nitride (TiAlN) to produce a black color, titanium carbide (TiC) to produce a gray color, zirconium nitride (ZrN) to produce a silver-yellow color, and hafnium nitride (HfN) to produce a yellow-green color.
  • [0077]
    The central sphere or other coats may be formed of a material that is heatable by remotely radiated energy for hyperthermia and/or a material that enables force to be applied to the seed to move it around using externally radiated energy to avoid damage to tissue. For example, ferrogmagnetic materials may be used that heat by induced radio frequency energy to the Curie temperature and have a Curie temperature appropriate for hyperthermia, such as for example, 50 degrees Centigrade. Moreover, a ferromagnetic material may cause movement of the seed by externally applied magnetic fields.
  • [0078]
    In one form of therapy using the multilayer radioactive microsphere, multiple low activity multilayer radioactive microsphere's (between 30 and 300) are permanently implanted into a human tumor at approximately 1 cm (centimeter) intervals throughout the volume, thus producing continuous low-dose-rate low energy irradiation at less than 1.0 Gy/hour and preferably less than 0.20 Gy/hour and delivering minimum doses of 80 to 400 Gy to the tumor volume over the average lifetime of the multilayer radioactive microsphere.
  • [0079]
    In another form of therapy using the multilayer radioactive microsphere (MRM), several (1 to 10) high activity multilayer radioactive microsphere's are permanently implanted into a human tumor producing continuous low-dose-rate low energy irradiation at less than 1.0 Gy/hour and preferably less than 0.20 Gy/hour and delivering minimum doses of 80 to 400 Gy to the tumor volume over the average lifetime of the multilayer radioactive microsphere.
  • [0080]
    In still another form of therapy, a long term low energy radiation is applied to a tumor followed by a short term high energy radiation. In one embodiment, the low energy radiation serves as a radioactive sensitizer which blocks tumor cells in the most radioactive sensitive portions of their cell cycles and the high energy beam is applied when the tumor cells are sensitive.
  • [0081]
    In one embodiment, a low intensity radioactive seed is implanted to provide the long term low intensity radioactivity and external radiation beam is used for the high intensity. In this embodiment, the relatively low radiation dose of between 40 to 80 Gray is delivered substantially continuously at a low dose rate over a time period of 30 to 200 days and preferably approximately 30 days. Either temporary or permanent implantation of one or several seeds may be used to accomplish this purpose. This low dose-rate radiation blocks the tumor cells in their most radioactive sensitive parts of their cell cycles. These are optimally killed at the time of delivery of a conventional daily fractionated radiation given over two minutes each 24-hour period for five days a week.
  • [0082]
    To avoid leakage of radioactive material, a layer of metal that chemically reacts with the material in the radioactive layer may be sputtered or otherwise coated over the radioactive material and before the defusion layer. For example, silver may be sputtered as an even coat over radioactive iodide layers to reduce leakage. The density and uniformity of the barrier layer is maximized by coating under the lowest pressure possible and by introducing maximum energy while avoiding welding of the microspheres together.
  • [0083]
    To make multilayer coatings of a microsphere for mass-production of the multilayer radioactive microsphere, a microspherical substrate is coated with multiple uniformly-spherical coats which consist of a radioactive coat, a thick protective coat (up to 0.1 millimeter), and in some embodiments, a diffusion barrier coat, an optional special-purpose imaging-enhancement coat and an optional special purpose outer thin coat.
  • [0084]
    The microsphere is adapted to be made in a manufacturing process that eliminates the need for assembly of separate seed parts and welding of titanium tubing containing the radioactive material because the multilayer radioactive microsphere is constructed by electronic means. In the processes used: (1) one-hundred to one-thousand multilayer radioactive microsphere's can be produced in a single batch or run of the coating equipment; and (2) the design of the multilayer radioactive microsphere can be easily modified or its components or type of radionuclide easily changed by changing either the target materials, coating atmosphere or operational parameters of the coating process.
  • [0085]
    In manufacturing the coats, existing coating techniques are used. In one embodiment, one or more radioactive dielectric or metal materials are used as a target in a sputter-deposition, laser ablation, or cathodic arc plasma-deposition system to produce a stable radioactive radionuclide-metal coat upon microspherical substrates, ribbon-mircospheres, or wire substrates. Moreover, combinations of radioactive and non-radioactive materials may be used.
  • [0086]
    The deposition of the radionuclide coat or laminate of a radionuclide and high-boiling point metal must be uniform. The peak-to-valley height variation in this coating should not exceed plus or minus 400 Angstroms. It should have high quality in terms of uniformity, spherosity and not have macroparticles, holes or other defects.
  • [0087]
    Other thin layers should be uniform but are not as sensitive to the lack of uniformity. Those layers are the diffusion barrier coat and in some embodiments, imaging coats. A relatively thick protective coat such as one of 0.05 millimeters is less critical as to uniformity.
  • [0088]
    All of these substrates are applied by processes which bond so there are substantially no voids in the member. Generally, sputtering is preferred with the thicker layers utilizing higher power and larger targets and the thinner layers smaller targets and lower power so that the same apparatus may be used for the different coats and all be applied with reasonable speed in spite of the difference of thicknesses by energizing different targets at different times. Thicker coats might also be applied by cathodic arc plasma-deposition techniques although these techniques do not usually apply with the same uniformity. In a few embodiments, electrolysis is suitable although electrolysis in most applications does not provide as uniform a surface area as sputtering and in the case of microspheres, it is difficult to obtain uniformity on all sides.
  • [0089]
    Generally, fabrics, wires and ribbons may be plated while they are suspended in a vacuum but the microspheres require a levitating device such as a vibrator that bounces them so that they will be coated on all sides. The most uniform coats are applied by vacuum methods but there are other methods which can create the uniformity and intimate contact of the coats desired in these products. Because some of the radionuclide coats are soft, low boiling point metals, special precautions can be taken to prevent the microspheres from being welded together. One such precaution is to combine the low boiling point radionuclide with a higher boiling point metal in interleaved areas or concomitantly. Injection of 1% to 5% of an electronegative gas such as oxygen gas will present microsphere vacuum welding. In another embodiment, gaseous radionuclides are bound by combining them with a metal during the coating process such as by sputtering the radioactive nuclide gas together with a metal in an argon atmosphere to form a coat of a compound combining the radionuclide and the metal.
  • [0090]
    The multilayer radioactive microsphere radio active microspherical substrate coat may be produced by one of several processes, such as: (1) from a radioactive metal target by dc sputtering; or (2) by radio frequency or magnetron sputtering using a radioactive dielectric target; or (3) by reactive sputter-deposition in an excited radioactive gas producing a coat which is a radioactive compound of the radioactive gas and the sputtered target material; or (4) by reactive cathodic arc plasma deposition in an excited radioactive gas producing a coat which is a radioactive compound of the radioactive gas and the sputtered target material; or (5) by reactive ion beam sputtering using a cathodic arc ion source in an excited radioactive gas producing a coat which is a radioactive compound of the radioactive gas and the sputtered target material; or (6) by reactive ion-plating using an electron-beam source in an excited radioactive gas producing a coat which is a radioactive compound of the radioactive gas and the sputtered target material; or (7) by cathodic arc plasma deposition using a radioactive dielectric target; or by (8) laser ablation of the target metal in the presence of a radioactive gas forming a radioactive metal compound on the substrate.
  • [0091]
    A radioactive dielectric coated planar metal target for use in cathodic arc plasma deposition or for use in rf or magnetron sputtering may be made by coating a metal planar substrate with a radio-active dielectric compound using reactive dc, rf, or magnetron sputtering, reactive cathodic arc plasma deposition, reactive ion-beam sputtering, or reactive ion plating wherein the radioactive compound coat is produced from an excited radionuclide gas and a non-radioactive metal target.
  • [0092]
    To optimize mass-production manufacture of the multilayer radioactive microsphere a two step process is used employing sputter deposition with a radioactive dielectric or metal target, or reactive sputter deposition in a radionuclide gas to produce a uniform radioactive coat over a microspherical substrate followed by ion-plating, or ion-beam self-sputtering using a cathodic arc ion source, or cathodic arc plasma deposition or high-energy high deposition rate sputtering using a large sputter gun, to produce the remaining coatings and spherical thick protective metal coatings over the radioactive microspheres.
  • [0093]
    In another method for mass-production manufacture of the multilayer radioactive microsphere consisting of a one-step process employing reactive cathodic arc plasma deposition, reactive laser ablation deposition, or reactive ion beam sputtering using a cathodic arc ion source, or reactive ion plating all carried out in an excited radionuclide reactive gas/inert gas mixture to form a smooth spherical stable compound radioactive coating over a microspherical substrate, followed by use of either ion plating, ion beam sputtering, cathodic arc deposition or laser ablation to produce the remaining coatings and spherical thick protective metal coatings over the radioactive microspheres.
  • [0094]
    In still another optimized method for mass-production manufacture of the multilayer radioactive microsphere consisting of a one-step process employing cathodic arc plasma deposition using a radioactive dielectric or metal target to produce a radioactive coat over a microspherical substrate, followed by use of cathodic arc plasma deposition to produce the remaining coats and spherical thick protective metal coats over the radioactive microspheres.
  • [0095]
    To eliminate vacuum welding between levitated microspheres, soft low boiling point elements (that are likely to vacuum weld) are laminated with hard, high boiling point elements (that are unlikely to vacuum weld). The microspherical substrates may be biased to improve reactive deposition efficiency using a reactive gas in a sputtering, ion plating, ion beam sputtering, or cathodic arc deposition. Moreover, levitation is improved to further reduce welding by creating a capacitive bias effect with the bouncing pan being electrically isolated from the rest of the sputtering apparatus. To create the capacitive bias effect, the bouncing pan may be an insulating ceramic with a conductive liner or may be a conductor coated with an insulating material. The material is connected by a conductor to a source of potential to create the bias. The bouncing pan is driven at high power by an ultrasonic transducer that is tuned to a frequency slightly different than the resonant frequency of the system.
  • [0096]
    Several embodiments of therapeutic devices can be formed. In one embodiment a ribbon-multilayer radioactive microsphere substrate has microspheres attached to the ribbon prior to coating. Coats are then applied to form a ribbon surface for rapid implanting of seeds. The coats may vary at different locations to enable in some embodiments, a contoured radiation pattern. In another embodiment, a multilayered radioactive wire design has a coat applied to a wire substrate by means of sputtering, laser ablation ion plating, ion beam sputtering, or cathodic arc deposition. The radioactive material is differentially deposited onto a substrate wire in such a manner that variable activities are deposited per unit length in a controlled fashion to match a computerized treatment plan.
  • [0097]
    In other embodiments, absorbable or non-absorbable surgical fabrics containing multiple multilayer radioactive microspheres spaced apart on the fabric or miniaturized intracavitary sources of radioactivity composed of multiple multilayer radioactive microsphere's are fabricated. Coats are applied in successive layers on the fabric and microsphere substrate or only on the microsphere substrate using masking in forming a fabric. Also, finished microspheres can be embedded during manufacture of a cellulose fabric. To form small intracavity sources, microspheres are first formed by sputtering or other such manufacturing technique and then after loaded into containers that are welded shut. In still another embodiment, an ocular applicator is constructed in which radioactive multilayers are deposited on the active surface by means of sputtering, ion plating, ion beam sputtering, cathodic arc deposition, or laser ablation.
  • [0098]
    Some of the embodiments that are fabricated enable improvement in other known techniques. For example, a modified multilayer radioactive microsphere that contains a ferromagnetic alloy that may be inductively heated in situ by applied radio frequency radiation may be formed. The coat passes through a Curie transition at temperatures useful for clinical hyperthermia and stops receiving inductive heating, thus maintaining the proper temperature. Also, a solid multilayered radioactive needle for temporary removable implants incorporates a wide variety of radionuclides and is thinner than a conventional radium-containing needle, thus enabling its use without major tissue trauma and improving the implant geometry.
  • [0099]
    The radioactive single seed design of this invention has several advantages such as: (1) it is smaller than prior art radioactive seeds and is spherical thus permitting a wider range of uses and easier use with less traumatic insertion into human tissues; (2) it is stronger and has high structural integrity and is thus safer; (3) it is symmetrical and uniform and thus produces a symmetrical radiation field as shown by symmetrical dosimetry; (4) it may be constructed using a wide variety of isotopes of differing energies and half-lives selected for specific applications, thus permitting optimization of the radiobiology of the type of cancer being treated; (5) it is inexpensive; and (6) in clinical practice, it permits safe delivery of radiation tumor doses that are two to five times higher than that achieved with external beam irradiation; and (7) the different multilayered radioactive microspheres can be identified by their different imaging contrast agent coats or center substrate.
  • [0100]
    In use, the microspheres have several advantages such as: (1) an effective modality for treatment is provided by combining a relatively low continuous dose of radiation by multilayer radioactive microspheres implanted in a tumor at any anatomic location and which serve as radio sensitizers so that a short conventional course of external-beam radiation therapy is much more effective; (2) radiation dose localization is improved beyond that achievable with the low energy permanent gamma-ray seeds by use of an electron-producing seed because electron dosimetry is more localized than X-ray dosimetry; (3) different types of multilayered radioactive microspheres with different half-lives and photon or electron energies can be implanted into a tumor in the same operation to optimize tumor therapy; and (4) the use of permanent implantation of short-lived seeds rather than temporary-removable implants eliminate exposed tubes which penetrate the skin surface and serve as a route for infection over many days.
  • [0101]
    There are also advantages from the composite designs that can be produced using the spheres, such as for example: (1) ribbons and a tissue-compatible fabric containing seeds useful for rapid surgical implantation may be produced; (2) the thin ribbon design containing multiple seeds allows rapid implantation of multiple seeds using a hollow interstitial needle; (3) a tissue-compatible surgical fabric containing multiple radioactive seeds allows rapid intraoperative implantation of a sheet of evently spaced radioactive seeds; and (4) the various surgical procedures and devices used for implantation of radioactive seeds provide better adaptability to a patient's needs.
  • [0102]
    There are also advantages from a wire multilayered radioactive design such as: (1) it may be cut up into pieces and placed into after loading catheters or into nylon or polyethylene ribbons for temporary removable implants or placed inside appropriate containers to construct various intracavitary sources; (2) it has the advantages of being flexible or remain as a long needle, with or without an added sleeve for temporary implanting.
  • [0103]
    When encapsulated: (1) the multilayered radioactive microspheres simplify intracavitary therapy because smaller intracavitary capsules can be construed using multiple small-diameter seeds of the present invention; (2) a wide variety of radionuclides with energies varying from very low to very high can be incorporated into composite intracivitary sources by sealing multiple multilayered radioactive microspheres of one or several types into an appropriate container; (3) use of low energy intracavitary sources composed of low energy multilayered radioactive microspheres allow selective shielding of adjacent vital structures such as rectum and bladder using relatively thin high atomic weight foils placed over the intracavitary sources or source holders.
  • [0104]
    There are also several advantages related to manufacturing the radioactive implants such as: (1) it permits mass production of a variety of designs without need of assembly of separate (radioactive) parts; (2) changes in seed composition may be made easily; (3) it permits customized manufacture of multilayered radioactive microspheres, multilayered radioactive wires, ribbon-multilayered radioactive microspheres or optical plaques optimized for individual tumor types; (4) manufacture of new models of multi-layered radioactive microspheres, multilayered radioactive wires and ribbon-multilayered radioactive microspheres can be accomplished as needed by simply changing deposition parameters, or by changing the type, thickness, and layering of deposited elements using the same deposition equipment; (5) it permits construction of seeds containing many optional different types of laminated materials such as imaging contrast agents, colored seed identification markers, or supplemental protective outer layers; (6) use of the high energy processes of sputtering, laser ablation ion-beam sputtering, cathodic arc or curvilinear cathodic arc plasma deposition, reactive deposition, and ion plating increase the hardness of metals coated in this manner compared to the bulk materials; and (7) the controlled variable deposition of radioactive material per unit length or per unit surface area permits customized manufacture of brachytherapy sources to exactly match the requirements of 3-dimensional computerized brachytherapy treatment plan.
  • [0105]
    The ability to provide a variety of half-lives and intensities of implants has several advantages, such as for example: (1) the smaller permanent seeds permit implantation of a greater number of seeds in more body sites using thinner needles with less risk of complication; (2) a combination of short-acting high-energy and long-acting low energy seeds can be implanted in the same procedure; (3) under some circumstances repeated implantation of seeds with short half-lives may be used instead of repeated temporary removable implant procedures thus reducing the risk of infection associated with temporary removable implants; (4) high energy short-lived seeds provide results equivalent to a temporary removable implant, but they may be applied to sites not accessible to temporary removable implantation; (5) short-lived seeds may be implanted as a “tumor-boost”, replacing and improving upon a “tumor-boost” delivered by means of external-beam radiation therapy; (6) with a wide variety of seeds available, many cancers can be more effectivley managed by brachytherapy alone; (7) a wide variety of radionuclides with energies varying from very low to very high can be incorporated into composite intracavitary sources by sealing multiple multilayered radioactive microspheres of one or several types into an appropriate container; (8) use of low energy intracavitary sources composed of low energy multilayered radioactive microspheres allow selective shielding of adjacent vital structures such as rectum and bladder using relatively thin high atomic weight foils placed over the intracavitary sources or source holders.
  • [0106]
    The ribbons, wire, plaques and fabric of this invention have the advantages of: (1) multiple multilayered radioactive microspheres provided on a single ribbon allow multiple multilayered radioactive microspheres to be implanted at once by a thin gauge hollow needle by pushing the multilayer radioactive microsphere ribbon out of the tissue-embedded needle with a stylet while withdrawing the needle; (2) the ribbon-multilayered radioactive microspheres of the present invention may be implanted by a very thin 21 or 22 -gauge needle; (3) the fabric of this invention self-adheres to the tissues over which it is placed and may be either tissue-absorbable or non-tissue absorbable; (4) the use of a fabric containing multiple multilayered radioactive microspheres allows rapid surgical implantation of multiple seeds without need of interstitial needles or a seed gun; and (5) very thin plaques such as optical plaques can be contoured have the appropriate strength and appropriate intensity for effective treatment.
  • SUMMARY OF THE DRAWINGS
  • [0107]
    The above noted and other features of the invention will be better understood from the following detailed description when considered with reference to the accompanying drawings in which:
  • [0108]
    [0108]FIG. 1 is a hemispherical sectional view of a multilayer radioactive microsphere in accordance with an embodiment of the invention;
  • [0109]
    [0109]FIG. 2 is a sectional view of another embodiment of a multilayer radioactive microsphere;
  • [0110]
    [0110]FIG. 3 is a sectional view of still another embodiment of multilayer radioactive microsphere;
  • [0111]
    [0111]FIG. 4 is a sectional view of still another embodiment of multilayer radioactive microsphere;
  • [0112]
    [0112]FIG. 5 is a sectional view of still another embodiment of multilayer radioactive microsphere;
  • [0113]
    [0113]FIG. 6 is a longitudinal sectional view of an embodiment of intracavitary radiation-emitting implant;
  • [0114]
    [0114]FIG. 7 is a perspective view of another embodiment of the invention formed as a wire or rod-like member;
  • [0115]
    [0115]FIG. 8 is a sectional elevational view of a ribbon-like embodiment;
  • [0116]
    [0116]FIG. 9 is a top sectional view of the embodiment of FIG. 8;
  • [0117]
    [0117]FIG. 10 is a plan view of an optical plaque in accordance with an embodiment of the invention;
  • [0118]
    [0118]FIG. 11 is a sectional view of the embodiment of FIG. 10 taken through lines 11-11;
  • [0119]
    [0119]FIG. 12 is a plan view of another embodiment of optical plaque in accordance with the invention;
  • [0120]
    [0120]FIG. 13 is a plan view of still another embodiment of optical plaque;
  • [0121]
    [0121]FIG. 14 is a plan view of still another embodiment of optical plaque;
  • [0122]
    [0122]FIG. 15 is a plan view of still another embodiment of optical plaque;
  • [0123]
    [0123]FIG. 16 is a plan view of still another embodiment of optical plaque;
  • [0124]
    [0124]FIG. 17 is a plan view of still another embodiment of optical plaque;
  • [0125]
    [0125]FIG. 18 is a plan view of a fabric-type embodiment of the invention;
  • [0126]
    [0126]FIG. 19 is a diagrammatic view of an eye showing a manner in which an embodiment of the invention is applied;
  • [0127]
    [0127]FIG. 20 is a diagrammatic view of an implant gun;
  • [0128]
    [0128]FIG. 21 is a schematic diagram of one embodiment of equipment for making microspheres;
  • [0129]
    [0129]FIG. 22 is a schematic diagram of another embodiment of apparatus for making microspheres;
  • [0130]
    [0130]FIG. 23 is a schematic diagram of still another embodiment of apparatus for making microspheres;
  • [0131]
    [0131]FIG. 24 is a schematic diagram of still another embodiment for making microspheres;
  • [0132]
    [0132]FIG. 25 is still another embodiment of apparatus for making microspheres;
  • [0133]
    [0133]FIG. 26 is still another embodiment of apparatus for making microspheres;
  • [0134]
    [0134]FIG. 27 is still another embodiment of apparatus for making microspheres;
  • [0135]
    [0135]FIG. 28 is still another embodiment of apparatus for making microspheres;
  • [0136]
    [0136]FIG. 29 is still another embodiment of apparatus for making microspheres;
  • [0137]
    [0137]FIG. 30 is a schematic diagram of an apparatus for preparing radiation-emitting ribbon;
  • [0138]
    [0138]FIG. 31 is a schematic diagram of another embodiment for producing variable deposition of radionuclide per unit length along elongated radiation-emitting members;
  • [0139]
    [0139]FIG. 32 is a schematic diagram of an embodiment of target assembly for use in an apparatus for making microspheres;
  • [0140]
    [0140]FIG. 33 is a front elevational view of a preferred embodiment for deposition of coats on microspheres;
  • [0141]
    [0141]FIG. 34 is a fragmentary side elevational view of the embodiment of FIG. 33;
  • [0142]
    [0142]FIG. 35 is a simplified enlarged elevational view of a chamber portion of the apparatus of FIG. 33;
  • [0143]
    [0143]FIG. 36 is a partly schematic, partly sectioned, fragmentary elevational view of a bouncing pan and driver therefor used in the embodiments of FIGS. 33-35; and
  • [0144]
    [0144]FIG. 37 is an exploded, partly sectioned, fragmentary elevational view of a bouncing pan structure used in the embodiments of FIGS. 33-36.
  • DETAILED DESCRIPTION
  • [0145]
    In FIG. 1, there is shown a sectional view of a radiation-emitting or radioactive microsphere 10 having a central sphere 12, and a layered section 14, with no space or voids between layers or between the central sphere 12 and the layered section 14 and no end-welds. It has an outside diameter less than 1 millimeter and provides a therapeutic amount of radiation selected in accordance with the desired treatment.
  • [0146]
    The central section is a microsphere and is normally solid but may be hollow. In the preferred embodiment, the material of which the central section is made is selected to serve as a substrate for other usefull coats applied over it, and under some circumstances, to serve other functions such as to identify or locate the implant. For this latter purpose, it may be selected to be opaque to radiation such as X-rays or easily detectable by other devices. If the central section 12 is itself the source of the therapeutic radiation, there may be a reduced number of layers in the layered section 14.
  • [0147]
    The center section or core 12 is less than 1 millimeter in diameter and in the preferred embodiment is generally 0.2 millimeters. However its size may be varied to accommodate different coating processes or to distinguish one radiation-emitting sphere from another by sensing the center section or the like. In the preferred embodiment the material is selected for its function.
  • [0148]
    This substrate center or core 12 may be made of a high atomic number metal or alloy such as iridium, platinum, gold, tantalum, tungsten or lead. Additionally, any lower atomic weight metal or alloy which is satisfactorily visualized on radiographs may be used including molybdenum, indium, lithium, silver, copper, and steel. Platinum, tantalum, gold, and silver are the preferred X-ray marker multilayer radiation-emitting microsphere core substrate materials in the present invention because of their high visibility on conventional radiographs.
  • [0149]
    In another seed design disclosed wherein only magnetic resonance imaging of the seed is clinically desirable and X-ray imaging is not necessary, the seed core 12 is composed of a non-metal such as carbon or diamond and an outer seed coat producing a magnetic resonance imaging signal (gadolinium) described below produces the seed image.
  • [0150]
    A multilayer radiation-emitting microsphere without a ferromagnetic core is essentially non-magnetic. This absence of ferromagnetic metal is advantageous for clinical situations where the implanted seed is implanted in close proximity to critical structures, such as near arterio-venous malformations in the brain. Here a strong magnetic field produced by magnetic resonance imaging equipment may exert enough force to dislodge or move a ferromagnetic metal-containing seed. A magnetically dislodged seed in the brain could cause immediate neurologic damage, stroke, or death of the patient. It could also be lost into the cerebrospinal fluid.
  • [0151]
    In the embodiment 10 of radiation-emitting microsphere of FIG. 1, the layered section 14 includes three layers 16, 18, and 20, in the order named, from the center section 12 outwardly. Each layer is concentric and they are selected in accordance with any of several therapeutic techniques. Other embodiments to be described hereinafter have still further coats and some embodiments may require primer coats to improve the ability to apply the layers to the central section or to each other or may require careful selection of techniques such as using mixtures of the material of the two coats at the interface between them.
  • [0152]
    Preferred primer metals include titanium, aluminum, tin, tantalum, vanadium, titanium nitride, titanium iodide, titanium oxide, titanium carbide, or metal alloys such as stainless steels or nickel alloys. If the coated material of one coat or the central section does not have good surface compatability with any primer metal, then a graded interface can be created composed of the materials of both coats or the central microsphere and its first coat as described below for a central substrate and a first coat that is a radioactive material.
  • [0153]
    The layer 16 may be an evenly distributed, highly-controlled, uniform, smooth, thin (less than 0.01 mm to 0.045 mm) spherical radiation-emitting coat that is produced by any method that results in a layer in intimate contact without void spaces. The material of the coat 16 may be any radiation-emitting material including: (1) a radionuclide with a weighted average gamma energy of less than 100 KeV, and with a half-life of less than 130 days for low energy permanent interstitial implantation; or (2) a radionuclide with a weighted average gamma energy greater than or equal to 100 KeV and with a half-life of less than 15 to 20 days for high-energy permanent interstitial implantation; or (3) a radionuclide that has a weighted average gamma energy greater than or equal to 100 KeV, with a half-life of greater than 15 to 20 days or an average energy less than 100 KeV and a half-life of greater than 130 days for temporary removable interstitial implantation; or (4) a radionuclide that emits a high energy electron particle without significant high-energy gamma-ray component for permanent or temporary removable interstitial implantation. It may be one metal, a mixture of metals, a dielectric compound, a mixture of dielectric compounds, a radionuclide that is normally a gas but is bound to a metal or other material in the radiation-emitting layer 16 or a plurality of layers of materials.
  • [0154]
    To provide the desired characteristics, the material of the layer 16 may be a metal selected from the group comprising palladium-103, gold-198, thulium-170, orchromium-56 or a combination of these or a dielectric radiation-emitting element such as arsenic-73, yttrium-90, or iodine-125 or a combination of these or a compound dielectric material containing one non-radiation-emitting and one radiation-emitting component with the radiation-emitting component such as zirconium iodide Zr(I-125)4, hafnium iodide Hf(I-125)4 titanium iodide Ti(I-125)2, silver 125iodide, thulium bromide-170, magnesium 73arsenide, potassium 125iodide, rubidium silver 125iodine, or copper 125iodide. It may include a radiation-emitting dielectric compound coat having two or more radiation-emitting components including any of arsenic-73 and di-iodide-125, arsenic-73, selenide-75, and palladium-103 iodide-125 or it may be laminated with a non-radiation-emitting and radiation-emitting materials. A list of such materials is provided in tables 1-19 of appropriate target materials and gases is provided in tables 20-58.
  • [0155]
    Moreover, instead of being a radiation-emitting microsphere from the start, the layer 16 may be formed of a material not in final form and altered by imparting radiation such as by nuclear or neutron bombardment or by combination with other layers of material under energy sources such as heat. For example, the microsphere in one stage of development may include a coat that is a non-radiation-emitting isotope precursor of the desired radiation-emitting isotope (such as those elements labelled with a * in tables 1-15). One such multilayer radiation-emitting microsphere may first contain a primary coat of non-radiation-emitting palladium-102 or samarium-144 but may be later irradiated with neutrons in a nuclear reactor or in a “neutron oven” to produce a finished multilayer radiation-emitting microsphere containing radiation-emitting palladium-103 or radiation-emitting samarium-145, respectively.
  • [0156]
    This material of layer 16 is atomically bound to the central section 12 and to the layer above it and in some cases such as sputtered metal layers and their nitrides, carbides or oxides, have hardness and durability that are several times higher than similar bulk metals. Generally, each layer is bound atomically to the material in the layers on either side of it.
  • [0157]
    The radiation emitting layer 16 may be a radiation emitting compound layer (such as thallium selenide-72, antimony telluride-19, uranium boride-231, zirconium carbide-86, copper iodide-125, Mo carbide-99, tantalum carbide-177, vanadium carbide-48, gallium telluride-67, indium telluride-125m, titanium iodide-125, or copper indium selenium-75) laminated with a hard metal (tantalum, tungsten, titanium, hafnium, zirconium, diamond-like carbon, niobium, osmium), metal compound (titanium nitride, titanium carbonitride, zirconium nitride, zirconium carbide, tantalum carbide, tungsten carbide, boron carbide, chromium dicarbide, hafnium carbide, hafnium oxide, lanthanum oxide, thorium carbide, vanadium carbide, hafnium nitride), or nonmetal (diamond or carbon) diffusion barrier. This laminated radiation-emitting coat uniformly covers the solid microspherical metal or carbon core (substrate).
    TABLE 1
    RADIONUCLIDES FOR LOW ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    As-73 80.3 days 53.4 KeV
    Se-72 8.4 days 46.0 KeV
    Pd-100 3.6 days 75-84 KeV
    *Pd-103 17.0 days 39.7 (0.02% 357 KeV)
    Pd-112 21.0 hours 18.5 KeV
    *Te-123m 117.0 days 88-159 KeV
    Te-127m 109.0 days 88.3 KeV
    Te-125m 58.0 days 35.5 KeV
    I-125 59.9 days 35.5 KeV
    *Ce-141 33.0 days 145 KeV
    *Nd-147 10.9 days 91.1 KeV
    (13% 531 KeV)
    Tb-151 17.6 hours 108-731 KeV
    Tb-155 5.3 days 86.5-105.3 KeV
  • [0158]
    [0158]
    TABLE 2
    RADIONUCLIDES FOR LOW ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Tb-161 6.9 days 25.6-74.6 KeV
    Dy-166 81.6 hours 82.5 KeV
    (0.5% 426 KeV)
    Ho-166 1.1 days 80.6 KeV
    (0.6% 1.4 MeV)
    *Er-168 9.4 days 8.42 KeV
    *Tm-170 128.6 days 84.3 KeV
    Sb-119 36.1 hours 23.9 KeV
    Lu-176m 3.6 hours 88.3 KeV
    *Os-191 15.0 days 49-186 KeV
    Hg-197 64.1 hours 77.4 KeV
    *Pt-195m 4.0 days 31-130 KeV
    Th-231 25.2 hours 25.6-84.2 KeV
    (0.2% 108 KeV)
    Th-234 24.1 days 63.3-92.7 KeV
    (0.3% 113 KeV)
  • [0159]
    [0159]
    TABLE 3
    RADIONUCLIDES FOR LOW ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Pu-237 45.1 days 59.5 KeV
    U-231 4.2 days 25.6 KeV (13%)
    84.2 KeV (6%)
    Tl-201 3.05 days Hg K-X-ray
  • [0160]
    [0160]
    TABLE 4
    RADIONUCLIDES FOR HIGH ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    K-43 22.3 hours 373 KeV
    As-74 17.8 days 595 KeV
    As-77 38.8 hours 239 KeV
    Sc-47 3.4 days 159 KeV
    Zr-86 16.5 hours 243 KeV
    In-111 2.8 days 170-245 KeV
    Sm-153 46.7 hours 103 KeV
    Sm-156 9.4 hours 87-204 KeV
    Eu-157 15.2 hours 64-413 KeV
    Gd-159 18.6 hours 364 KeV
    Pb-203 2.2 days 279 KeV
    V-48 15.9 days 984 KeV
    Cr-48 21.6 hours 116-305 KeV
    *Fe-52 8.2 hours 168-377 KeV
  • [0161]
    [0161]
    TABLE 5
    RADIONUCLIDES FOR HIGH ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Cu-67 61.9 hours 91.2-184 KeV
    Zn-62 9.3 hours 41.0-596 KeV
    Ga-67 78.3 hours 93.0-394 KeV
    Ga-73 4.9 hours 297 KeV
    Se-73 7.1 hours 67.0-361 KeV
    Br-77 57.0 hours 87.0-818 KeV
    *As-76 26.5 hours 559- KeV
    Kr-76 14.8 hours 45.5-452 KeV
    Rb-81 4.6 hours 190-446 KeV
    Sr-83 32.4 hours 763 KeV
    Y-87 80.3 hours 388 KeV
    Mo-99 65.9 hours 144-739 KeV
    Ru-97 2.9 days 216-461 KeV
    Rh-105 35.4 hours 306-319 KeV
    Cd-107 6.5 hours 93-829 KeV
    Cd-115 53.5 hours 336-528 KeV
    Sn-110 4.0 hours 283 KeV
    *Sn-117m 14.0 days 159 KeV
  • [0162]
    [0162]
    TABLE 6
    RADIONUCLIDES FOR HIGH ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Te-119 16.0 hours 644 KeV
    Te-132 78.2 hours 49.7-228 KeV
    Cs-127 6.2 hours 412 KeV
    Cs-129 32.3 hours 371-412 KeV
    Ag-111 7.5 days 250-340 KeV
    Te-121 16.8 days 573 KeV
    I-131 8.0 days 364 KeV
    Ba-128 2.4 days 273 KeV
    Ba-131 11.8 days 496 KeV
    Ba-140 12.8 days 162-537 KeV
    *Ce-141 33.0 days 145 KeV
    Ce-134 76.0 hours 605 KeV
    Ce-137 9.0 hours 447 KeV
    Nd-138 5.1 hours 199-326 KeV
    Pm-151 28.4 hours 3400 KeV
    Tb-155 5.3 days 86.5-105.3 KeV
  • [0163]
    [0163]
    TABLE 7
    RADIONUCLIDES FOR HIGH ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Dy-157 8.1 hours 182-326 KeV
    Yb-175 4.19 days 114-396 KeV
    Os-182 21.5 hours 131-510 KeV
    Os-191 15.4 days 129.4 KeV
    Pt-184 10.2 days 188-423 KeV
    Pr-143 13.6 days 742 KeV
    Eu-157 15.2 hours 413 KeV
    Gd-149 9.3 days 149-346 KeV
    Er-169 9.4 days 109-118 KeV
    Tm-167 9.2 days 208 KeV
    Tm-173 8.2 hours 398-461 KeV
    Yb-175 4.2 days 114-396 KeV
  • [0164]
    [0164]
    TABLE 8
    RADIONUCLIDES FOR HIGH ENERGY PERMANANENT
    MULTILAVERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Hf-170 16.0 hours 593-621 KeV
    Hf-171 12.1 hours 122-1,071 KeV
    Hf-173 23.6 hours 123.6-311.2 KeV
    Hf-184 4.1 hours 139-345 KeV
    Re-181 20.0 hours 177-365 KeV
    Re-188 16.9 hours 155 KeV
    Re-189 24.0 hours 148-563 KeV
    Lu-177 6.7 days 113-332 KeV
    Lu-179 4.6 hours 214 KeV
    Ta-177 2.4 days 113 KeV
    Ta-180m 8.2 hours 93.3-103 KeV
    Ta-183 5.1 days 246-354 KeV
    W-187 23.9 hours 479-685 KeV
    Ir-189 13.2 days 245 KeV
    Pt-191 2.9 days 82.4-539 KeV
    Pt-197 18.3 hours 191.4 KeV
    Pt-200 12.5 hours 135-330 KeV
  • [0165]
    [0165]
    TABLE 9
    RADIONUCLIDES FOR HIGH ENERGY PERMANANENT
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Au-193 17.6 hours 112-439 KeV
    *Au-198 2.7 days 412 KeV
    Au-199 3.1 days 158-208 KeV
    Hg-192 4.9 hours 275 KeV
    Hg-195m 40.0 hours 262 KeV
    Hg-197m 23.8 hours 134 KeV
    Tl-201 3.0 days 135-165 KeV
    Tl-202 12.2 days 439 KeV
    Pb-100 21.5 hours 148 KeV
    Nb-90 14.6 hours 141-2,319 KeV
    Nb-92m 10.1 days 934 KeV
    Nb-96 23.4 hours 460-1,202 KeV
    Bk-245 4.9 days 253 KeV
    Bk-246 1.8 days 799 KeV
    Es-254m 1.64 days 648-693 KeV
    U-237 6.75 days 59.0 KeV (33%)
    208.0 KeV (22%)
  • [0166]
    [0166]
    TABLE 10
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life greater
    than 15 days, or Energy less than 100 KeV and
    Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Be-7 53.3 days 477 KeV
    Sc-46 83.3 days 159 KeV
    As-74 17.8 days 595 KeV
    *Se-75 120.4 days 135-264 KeV
    Co-57 271.0 days 122 KeV
    Rb-83 86.2 days 521-529 KeV
    Sr-85 64.8 days 514 KeV
    Ti-44 47.0 years 67.8-78.4 KeV
    Se-75 118.5 days 136-264 KeV
    Zr-88 83.4 days 393 KeV
    Zr-93 1.5 × 106 years 30.4 KeV
    *Zr-95 64.0 days 724-756 KeV
    La-138 1.06 × 1011 years 788-1,436 KeV
    Gd-146 48.3 days 115-155 KeV
    Nb-92 3 × 107 years 61-935 KeV
    Nb-93m 13.6 years 30.4 KeV
    Nb-94 2.4 × 104 years 703-871 KeV
    Nb-95 34.9 days 766 KeV
    *Mo-93 3.5 × 103 years 30.4 KeV
  • [0167]
    [0167]
    TABLE 11
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life greater
    than 15 days, or Energy less than 100 KeV and
    Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Cr-51 27 days 320 KeV
    *Cd-109 450 days 88 KeV
    *Cd-115m 43 days 935 KeV
    *In-114m 50 days 191-724 KeV
    *Sn-119m 250 days 23-65 KeV
    *Sn-121m 76 years 37 KeV
    *Sb-124 60 days 443 KeV
    *Te-129m 34 days 487-696 KeV
  • [0168]
    [0168]
    TABLE 12
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    *Ru-103 39.3 days 497 KeV
    *Ag-107 5.0 years 30-722 KeV
    Sb-125 2.8 years 427-636 KeV
    I-129 1.6 × 107 years 39.6 KeV
    *Cs-134 2.0 years 604-795 KeV
    Cs-137 30.2 years 662 KeV
    Ce-144 284.4 days 134 KeV
    Pm-143 265.0 days 742 KeV
    Pm-145 17.7 years 67.2 KeV
    *Sm-145 340.0 days 61.3 KeV
    *Sm-151 93.0 years 298 KeV
    Eu-155 4.7 years 105 KeV
    Gd-153 241.6 days 69-103 KeV
    Dy-159 144.0 days 326 KeV
    *Tb-160 73.0 days 298 KeV
    *Tm-171 1.9 years 66.7 KeV
    Lu-173 1.4 years 78-271 KeV
    Lu-174 3.3 years 76.6 KeV
    Hf-172 1.87 years 23.9-125 KeV
  • [0169]
    [0169]
    TABLE 13
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Hf-175 70.0 days 343 KeV
    *Hf-178m2 31.0 years 88.8-426 KeV
  • [0170]
    [0170]
    TABLE 14
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Hf-179m2 25.1 days 123-453 KeV
    *Hf-181 42.4 days 133-482 KeV
    *Hf-182 9 × 106 years 114-270 KeV
    *W-185 74.8 days 125 KeV
    W-188 69.4 days 63.6-291 KeV
    Yb-169 32.0 days 63.0-307 KeV
    Re-183 70.0 days 163 KeV
    Os-194 6.0 years 42.9 KeV
    *Ir-192 73.8 days 205-604 KeV
    Ir-194m 171.0 days 328-688 KeV
    *Hg-203 46.6 days 279 KeV
    Am-241 432.2 years 59.5 KeV
    *Bi-210M 1000.0 years 300 KeV
    Am-242m 141.0 years 86.5 KeV
    *Am-243 7.4 × 103 years 74.7 KeV
    Cm-241 32.8 days 472 KeV
    Cm-243 28.5 years 228 KeV
    Cm-245 8.5 × 103 years 174 KeV
  • [0171]
    [0171]
    TABLE 15
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    Bk-247 1.4 × 103 years 83.9-268 KeV
    Cf-249 351 years 388 KeV
  • [0172]
    [0172]
    TABLE 16
    RADIONUCLIDES FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    RADIONUCLIDE HALF-LIFE MAIN GAMMA ENERGIES
    U-233 1.59 × 105 years 42-97 KeV
    U-234 2.45 × 105 years 53 KeV
    (0.04% 121 KeV)
    U-235 7.04 × 108 years 185.7 KeV
    U-236 2.34 × 107 years 49.4-112.7 KeV
    *U-238 4.46 × 109 years 49.5 KeV
  • [0173]
    [0173]
    TABLE 17
    RADIONUCLIDES FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    RADIO- GAMMA
    NUCLIDE HALF-LIFE PARTICLE ENERGY COMPONENT
    Si-32 100.0 years beta − 213 KeV
    P-32 14.3 days beta − 1.71 MeV
    P-33 25.3 days beta − 249 KeV
    Cl-36 3.0 × 105 years beta − 0.71 MeV
    K-40 1.3 × 109 years beta − 1.31 MeV annihilation rad
    1.4 MeV 10%
    K-42 12.4 hours beta − 3.52 MeV 1.5 MeV 18.9%
    Ca-45 163.8 days beta − 257 KeV
    Ti-45 3.1 hours beta + 1.04 MeV annihilation rad
    Cu-64 12.7 hours beta − 578 KeV annihilation rad
    beta + 650 KeV 1.3 MeV 0.6%
    Bi-210 5.0 days beta − 1.16 MeV
    Sr-89 50.5 days beta − 1.49 MeV 0.9 MeV 0.0009%
    Sr-90 29.0 years beta − 546 KeV
    S-35 87.2 days beta = 167 KeV
  • [0174]
    [0174]
    TABLE 18
    RADIONUCLIDES FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    RADIO-
    NUCLIDE HALF-LIFE PARTICLE ENERGY GAMMA COMPONENT
    Y-90 64.0 hours beta − 2.28 MeV
    Zr-89 78.4 hours beta + 0.90 MeV annihilation
    rad
    1.7 MeV
    0.7%
    Pd-112 21.0 hours beta − 280 KeV 18.5 KeV
    27%
    Ag-111 7.47 days beta − 1.0 MeV 0.34 MeV
    6.7%
    Cd-113m 13.7 years beta − 590 KeV 264 KeV
    0.02%
    Cd-115m 44.6 days beta − 1.62 MeV 1.2 MeV
    0.9%
    In-115 4.4 × 1014 years beta − 348 KeV
    Sn-123 129.2 days beta − 1.42 MeV 1.08 MeV
    0.6%
    Cs-135 3.0 × 106 years beta − 205 KeV
    Pr-139 4.4 hours beta + 1.1 MeV annihilation
    rad
    1.6 MeV
    0.3%
    Pr-143 13.6 days beta − 935 KeV 742 KeV
    0.00001%
    Er-169 9.6 days beta = 340 KeV
  • [0175]
    [0175]
    TABLE 19
    RADIONUCLIDES FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    RADIO- GAMMA
    NUCLIDE HALF-LIFE PARTICLE ENERGY COMPONENT
    Ho-166 1.1 days beta − 1.8 MeV 80.5 KeV 6.0%
    1.3 MeV 0.90%
    Tm-170 128.6 days beta − 883 KeV 84.3 KeV 3.3%
    Yb-175 4.2 days beta − 467 KeV 396 KeV 6.5%
    Lu-177 6.7 days beta − 497 KeV 208 KeV 11%
    W-185 74.8 days beta − 433 KeV 125 KeV 0.019%
    W-188 69.4 days beta − 349 KeV 291 KeV 0.40%
    *Tl-204 3.8 years beta − 763 KeV
    *Bi-210 5.0 days beta − 1.2 MeV
    Th-231 25.2 hours beta − 305 KeV 25.6 KeV 15%
    84.2 KeV 6.6%
    Th-234 24.1 days beta − 198 KeV 63.3 KeV 3.8%
    92.4 KeV 2.7%
    Re-186 3.7 days beta = 1.07 MeV
  • [0176]
    [0176]
    TABLE 20
    MANUFACTURING PARAMETERS FOR LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    As-73 AS-73 Ar As-73
    As-73 Ar As-73 Tribromide
    Tribromide
    As-73 Ar/Oxygen As-73 Trioxide
    As-73 Ar/Hydrogen As-73 Trisulfide
    Sulfide
    Gallium Ar/As-73H3 GaAs-73
    Cobalt Ar/As-73H3 Co2As-73
    Nickel Ar/As-73H3 NiAs-73
    Indium Ar/As-73H3 InAs-73
    Iron Ar/As-73H3 FeAs-73
    Tungsten Ar/As-73H3 W(As-73)2
    Se-72 Se-72 Ar Se-72
    Se-72 Ar/Acetylene Se-72 Carbide
    Se-72 Ar/Nitrogen Se-72 Nitride
    Se-72 Ar/Oxygen Se-72 Oxide
    Se-72 Ar/Hydrogen Se-72 Sulfide
    Sulfide
    Iridium Ar/H2Se-72 Ir(Se-72)2
    Indium Ar/H2Se-72 In2(Se-72)3
    Thallium Ar/H2Se-72 Tl2Se-72
  • [0177]
    [0177]
    TABLE 21
    MANUFACTURING PARAMETERS FOR LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Pd-100 Pd-100 Ar Pd-100
    *Pd-103 Pd-103 same as
    Pd-100
    Pd-112 Pd-112 same as
    Pd-100
    Te-123m Te-123m same as
    Te-125m
    Te-125m Te-125m Ar Te-125m
    Te-125m Ar/Oxygen Te-125O3
    Gallium Ar/H2Te-125 GaTe-125
    Lead Ar/H2Te-125 PbTe-125
    Indium Ar/H2Te-125 InTe-125
    Platinum Ar/H2Te-125 Pt(Te-125)2
    Te-127m Te-127m same as
    Te-125m
    I-125 CuI-125 Ar Copper
    iodide-125
    AgI-125 Ar Silver
    iodide-125
    KI-125 Ar Potassium
    iodide-125
    Ti(I-125)2 Ar Titanium
    di-iodide-125
    Zr(I-125)4 Ar Zirconium
    iodide-125
    Hf(I-125)4 Ar Hafnium
    iodide-125
    Cr(I-125)2 Ar Chromium
    iodide-125
    Dy(I-125)3 Ar Dysprosium
    iodide-125
    Er(I-125)3 Ar Erbium
    iodide-125
  • [0178]
    [0178]
    TABLE 22
    MANUFACTURING PARAMETERS FOR LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    I-125 (continued)
    Eu(I-125)2 Ar Europium
    iodide-125
    Ho(I-125)3 Ar Holmium
    iodide-125
    Li(I-125) Ar Lithium
    iodide-125
    Lu(I-125)3 Ar Lutetium
    iodide-125
    Nd(I-125)3 Ar Neodymium
    iodide-125
    Rb(I-125) Ar Rubidium
    iodide-125
    Sm(I-125)2 Ar Samarium
    iodide-125
    Tb(I-125)3 Ar Terbium
    iodide-125
    Titanium Ar/(I-125)2 Titanium
    di-iodide-125
    Ar/HI-125
    Zirconium Ar/(I-125)2 Zirconium
    iodide-125
    Ar/HI-125
    Hafnium Ar/(I-125)2 Hafnium
    iodide-125
    Ar/HI-125
    Chromium Ar/(I-125)2 Chromium
    iodide-125
    Ar/Hi-125
    Dysprosium Ar/(I-125)2 Dysprosium
    iodide-125
    Ar/HI-125
    Erbium Ar/(I-125)2 Erbium
    iodide-125
    Ar/HI-125
    Europium Ar/(I-125)2 Europium
    iodide-125
    Ar/HI-125
  • [0179]
    [0179]
    TABLE 23
    MANUFACTURING PARAMETERS FOR LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Holmium Ar/(I-125)2 Holmium
    iodide-125
    Ar/HI-125
    Lithium Ar/(I-125)2 Lithium
    iodide-125
    Ar/HI-125
    Lutetium Ar/(I-125)2 Lutetium
    iodide-125
    Ar/HI-125
    Neodymium Ar/(I-125)2 Neodymium
    iodide-125
    Ar/HI-125
    Rubidium Ar/(I-125)2 Rubidium
    iodine-125
    Ar/HI-125
    Samarium Ar/(I-125)2 Samarium
    iodine-125
    Ar/HI-125
    Terbium Ar/(I-125)2 Terbium
    iodine-125
    Ar/HI-125
    *Ce-141 Ce-141
    Ce-141 same as
    fluoride Ce-134
    *Nd-147 Nd-147 Ar Nd-147
    Nd-147 Ar Nd-147 bromide
    bromide
    Nd-147 Ar Nd-147 fluoride
    fluoride
    Nd-147 Ar/Acetylene Nd-147 carbide
    Nd-147 Ar/Nitrogen Nd-147 nitride
    Nd-147 Ar/Oxygen Nd-147 oxide
    Nd-147 Ar/Hydrogen Nd-147 sulfide
    Sulfide
  • [0180]
    [0180]
    TABLE 24
    MANUFACTURING PARAMETERS FOR LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies Less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Tb-155 Tb-155 Ar Tb-155
    Tb-155 Ar Tb-155 bromide
    bromide
    Tb-155 Ar Tb-155 fluoride
    fluoride
    Tb-155 Ar/Oxygen Tb-155 oxide
    Tb-161 Tb-161 same as
    Tb-155
    Tb-161
    bromide
    Tb-161
    fluoride
    Tb-161
    Dy-166 Dy-166 Ar Dy-166
    Dy-166 Ar Dy-166 bromide
    bromide
    Dy-166 Ar Dy-166 chloride
    chloride
    Dy-166 Ar Dy-166 fluoride
    fluoride
    Dy-166 Ar/Oxygen Dy-166 oxide
    Ho-166 Ho-166 Ar Ho-166
    Ho-166 Ar Ho-166 bromide
    bromide
    Ho-166 Ar Ho-166 chloride
    chloride
    Ho-166 Ar/Oxygen Ho-166 oxide
    *Er-168 Er-168
    Er-168 same as
    fluoride Er-169
    *Tm-170 Tm-170 Ar Tm-170
    Tm-170 Ar Tm-170 bromide
    bromide
    Tm-170 Ar Tm-170 fluoride
    fluoride
    Tm-170 Ar/Oxygen Tm-170 oxide
    Lu-176m Lu-176m same as
    Lu-177
    Lu-176m
    fluoride
  • [0181]
    [0181]
    TABLE 25
    MANUFACTURING PARAMETERS OF LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Sb-119 Sb-119 Ar Sb-119
    Tellurium Ar/Sb-119H3 (Sb-119)2Te3
    Indium Ar/Sb-119H3 InSb-119
    *Pt-195m Pt-195m same as
    Pt-184
    Pt-195M
    phosphide
    Hg-197 Hg-197 Ar Hg-197 fluoride
    fluoride
    Hg-197 Ar/Oxygen Hg-197 oxide
    Tl-201 Tl-201 Ar Tl-201
    Th-231 Th-231 Ar Th-231
    Th-231 Ar Th-231 hexaboride
    hexaboride
    Th-231 Ar/Acetylene Th-231 carbide
    Th-231 Ar/Oxygen Th-231 oxide
    Th-231 Ar/Hydrogen Th-231 sulfide
    Sulfide
    Th-231 Ar/B2H6
    Th-234 Th-234 same as
    Th-231
    Th-234
    hexaboride
    Th-234
    Th-234
    Th-234
    Th-234
  • [0182]
    [0182]
    TABLE 26
    MANUFACTURING PARAMETERS FOR LOW ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies less than 100 KeV,
    Half-Life less than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Pu-237 Pu-237 Ar Pu-237
    U-231 U-231 Ar U-231
    U-231 Ar/B2H6 U-231B2
    Boron Ar/U-231F6 U-231B2
  • [0183]
    [0183]
    TABLE 27
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS
    As-74 As-74 same as As-73
    As-74 Tribromide
    As-74
    As-74
    Gallium
    Cobalt
    Nickel
    Indium
    Iron
    Tungsten
    As-77 As-77 same as As-73
    As-77 Tribromide
    As-77
    As-77
    Gallium
    Cobalt
    Nickel
    Indium
    Iron
    Tungsten
    Sc-47 Sc-47 Ar
  • [0184]
    [0184]
    TABLE 28
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Zr-86 Zr-86 Ar Zr-86
    Zr-86 Ar Zr-86 diboride
    diboride
    Zr-86 Ar/Acetylene Zr-86 carbide
    Zr-86 Ar/Nitrogen Zr-86 nitride
    Zr-86 Ar/Oxygen Zr-86 oxide
    Zr-86 Ar/Hydrogen Zr-86 sulfide
    Sulfide
    Zr-86 Ar/B2H6 Zr-86 diboride
    Graphite Ar/Zr-86Cl4 Zr-86 carbide
    Boron AR/Zr-86Cl4 Zr-86 diboride
    Sm-153 Sm-153 Ar Sm-153
    Sm-153 Ar Sm-153 bromide
    bromide
    Sm-153 Ar Sm-153 fluoride
    fluoride
    Pb-203 Pb-203 Ar Pb-203
    Pb-203 Ar Pb-203 fluoride
    fluoride
    V-48 V-48 Ar V-48
    V-48 Ar/Acetylene V-48 carbide
    V-48 Ar/Nitrogen V-48 nitride
    V-48 Ar/Oxygen V-48 oxide
    V-48 Ar/Hydrogen V-48 sulfide
    Sulfide
    V-48 Ar/B2H6 V-48B2
    Graphite Ar/V-48F5 V-48 carbide
    Boron Ar/V-48Cl4 V-48B2
  • [0185]
    [0185]
    TABLE 29
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Cu-67 Cu-67 Ar Cu-67
    Cu-67 Ar Cu-67 fluoride
    fluoride
    Cu-67 Ar/Oxygen Cu-67 oxide
    Ga-67 Ga-67 Ar Ga-67
    Tellurium Ar/Ga-67Cl3 Ga-67
    telluride
    Br-77 Samarium Ar Samarium
    (Br-77)2 (Br-77)2
    Neodymium Ar Neodymium
    (Br-77)3 (Br-77)3
    Sr-83 Sr-83 Ar Sr-83
    Sr-83 Ar/Oxygen Sr-83 oxide
    Sr-83 Ar/Acetylene Sr-83 carbide
    Y-87 Y-87 Ar Y-87
    Y-87 Ar Y-87 chloride
    chloride
  • [0186]
    [0186]
    TABLE 30
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Mo-99 Mo-99 Ar Mo-99
    Mo-99 Ar/Acetylene Mo-99 carbide
    Graphite Ar/Mo-99Cl5 Mo-99 carbide
    Graphite Ar/Mo-99F6 Mo-99 carbide
    Ru-97 Ru-97 Ar Ru-97
    Rh-105 Rh-105 Ar Rh-105
    Cd-115 Cd-115 Ar Cd-115 fluoride
    fluoride
    Cd-115 Ar/Oxygen Cd-115 oxide
    Cd-115 Ar/Hydrogen Cd-115 sulfide
    Sulfide
    *Sn-117m Sn-117m same as Sn-123
    Tellurium
    Te-132 Te-132 Ar Te-132
    Te-132 Ar/Oxygen Te-132 oxide
    Gallium Ar/Te-132H2 GaTe-132
    Lead Ar/Te-132H2 PbTe-132
    Indium Ar/Te-132H2 InTe-132
    Platinum Ar/Te-132H2 Pt(Te-132)2
    Cs-129 Cs-129 Ar Cs-129 bromide
    bromide
    Cs-129 Ar Cs-129 chloride
    chloride
    Cs-129 Ar Cs-129 fluoride
    fluoride
    Cs-129 Ar Cs-129 iodide
    iodide
  • [0187]
    [0187]
    TABLE 31
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Ag-111 Ag-111 Ar Ag-111
    Ag-111 chloride Ar Ag-111 chloride
    Ag-111 iodide Ar Ag-111 iodide
    Tellurium Ar/Ag-111N3 (Ag-111)2Te
    HgI2 Ar/Ag-111N3 (Ag-111)2HgI4
    Te-121 Te-121 same as Te-132
    Te-121
    Gallium
    Lead
    Indium
    Platinum
    I-131 CuI-131 same as I-125
    AgI-131
    KI-131
    Ti(I-131)2
    Zr(I-131)4
    Hf(I-131)4
    Cr(I-131)2
    Dy(I-131)3
    Er(I-131)3
    Eu(I-131)2
    Ho(I-131)3
  • [0188]
    [0188]
    TABLE 32
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    I-131 Li(I-131) same as I-125
    Lu(I-131)3
    Nd(I-131)3
    Rb(I-131)
    Sm(I-131)2
    Tb(I-131)3
    Titanium
    Zirconium
    Hafnium
    Chromium
    Dysprosium
    Erbium
    Europium
    Holmium
    Lithium
    Lutetium
    Neodymium
    Rubidium
    Samarium
    Terbium
  • [0189]
    [0189]
    TABLE 33
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Ba-128 Ba-128 chloride Ar Ba-128 chloride
    Ba-128 fluoride Ar Ba-128 fluoride
    Ba-128 Ar/Oxygen Ba-128 oxide
    Ba-131 Ba-131 chloride same as Ba-128
    Ba-131 fluoride
    Ba-128
    Ba-140 Ba-140 chloride same as Ba-128
    Ba-140 fluoride
    Ba-140
    Ce-134 Ce-134 Ar Ce-134
    Ce-134 fluoride Ar Ce-134 fluoride
    Ce-134 Ar/Oxygen Ce-134 oxide
    Nd-138 Nd-138 same as Nd-147
    Nd-138 bromide
    Nd-138 fluoride
    Nd-138
    Nd-138
    Nd-138
    Nd-138
    *Ce-141 Ce-141 same as Ce-134
    Ce-141 fluoride
  • [0190]
    [0190]
    TABLE 34
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Pm-151 Pm-151 Ar Pm-151
    Tb-155 see previous Tb-155 entry
    Dy-157 Dy-157 same as Dy-166
    Dy-157 bromide
    Dy-157 chloride
    Dy-157 fluoride
    Dy-166
    Yb-175 Yb-175 Ar Yb-175
    Yb-175 bromide Ar Yb-175 bromide
    Yb-175 fluoride Ar Yb-175 fluoride
    *Os-191 Os-191 Ar Os-191
    Pt-184 Pt-184 Ar Pt-184
    Pt-184 phosphide Ar Pt-184 phosphide
    Pr-143 Pr-143 Ar Pr-143
    Pr-143 fluoride Ar Pr-143 fluoride
    Pr-143 Ar/Oxygen Pr-143 oxide
  • [0191]
    [0191]
    TABLE 35
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Gd-149 Gd-149 Ar Gd-149
    Gd-149 iodide Ar Gd-149 iodide
    Er-169 Er-169 Ar Er-169
    Er-169 fluoride Ar Er-169 fluoride
    Tm-167 Tm-167 same as Tm-170
    Tm-167 bromide
    Tm-167 fluoride
    Tm-167
    Hf-170 Hf-170 Ar Hf-170
    Hf-170 Ar/Acetylene Hf-170 carbide
    Hf-170 Ar/Nitrogen Hf-170 nitride
    Hf-170 Ar/Oxygen Hg-170 oxide
    Hf-171 Hf-171 same as Hf-170
    Hf-171
    Hf-171
    Hf-171
    Hf-173 Hf-173 same as Hf-170
    Hf-173
    Hf-173
    Hf-173
  • [0192]
    [0192]
    TABLE 36
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Hf-184 Hf-184 same as Hf-170
    Hf-184
    Hf-184
    Hf-184
    Re-181 Re-181 Ar Re-181
    Re-188 Re-188 same as Re-181
    Re-189 Re-189 same as Re-181
    Lu-177 Lu-177 Ar Lu-177
    Lu-177 fluoride Ar Lu-177 fluoride
    Ta-177 Ta-177 Ar Ta-177
    Ta-177 Ar/Acetylene Ta-177 carbide
    Ta-177 Ar/B2H6 Ta-177 boride
    Boron Ar/Ta-177F8 Ta-177 boride
    Graphite Ar/Ta-177F8 Ta-177 carbide
    Ta-180m Ta-180m same as Ta-177
    Ta-180m
    Ta-180m
    Boron
    Graphite
  • [0193]
    [0193]
    TABLE 37
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Ta-183 Ta-183 same as Ta-177
    Ta-183
    Ta-177
    Boron
    Graphite
    W-187 W-187 Ar W-187
    W-187 Ar/Acetylene W-187 carbide
    W-187 Ar/B2H6 W-187 Boride
    Boron Ar/W-187Cl5 W-187 Boride
    Graphite Ar/W-187F6 W-187 carbide
    Ir-189 Ir-189 Ar Ir-189
    Pt-191 Pt-191 same as Pt-184
    Pt-191 phosphide
    Au-193 Au-193 Ar Au-193
    Tellurium Ar/Au-193Cl2 Au-193Te2
    *Au-198 Au-198 same as Au-193
    Tellurium
  • [0194]
    [0194]
    TABLE 38
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Au-199 Au-199 same as Au-193
    Tellurium
    Hg-195m Hg-195m fluoride same as Hg-197
    Hg-195m
    Hg-197m Hg-197m fluoride same as Hg-197
    Hg-197m
    Tl-201 Tl-201 Ar Tl-201
    Vanadium Ar/O2/Tl-201NO3 Tl201VO3
    Tl-202 Tl-202 same as Tl-201
    Vanadium
    Pb-100 Pb-100 same as Pb-203
    Pb-100 fluoride
    Nb-90 Nb-90 Ar Nb-90
    Nb-90 Ar/Acetylene Nb-90 carbide
    Nb-90 Ar/B2H6 Nb-90 boride
    Boron Ar/Nb-90Cl5 Nb-90 boride
    Graphite Ar/Nb-90F5 Nb-90 carbide
  • [0195]
    [0195]
    TABLE 39
    MANUFACTURING PARAMETERS FOR HIGH ENERGY
    PERMANANENT MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Main Gamma Energies greater than 100 KeV,
    Half-Life Less than 15 to 20 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Nb-92m Nb-92 same as Nb-90
    Nb-92
    Nb-92
    Boron
    Graphite
    Nb-96 Nb-96 same as Nb-90
    Nb-96
    Nb-96
    Boron
    Graphite
    Bk-245 Bk-245 Ar Bk-245
    Bk-246 Bk-246 same as Bk-245
    Bk-247 Bk-247 same as Bk-245
    Cf-249 Cf-249 Ar Cf-249
    Es-254m Es-245m Ar Es-254m
    U-237 U-237 same as U-231
    U-237
    Boron
  • [0196]
    [0196]
    TABLE 40
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Be-7 Be-7 Ar Be-7
    Be-7 Ar/Nitrogen Be-7 nitride
    Be-7 Ar/Oxygen Be-7 oxide
    Be-7 Ar/Acetylene Be-7 oxide
    Sc-46 Sc-46 same as Sc-47
    Co-57 Co-57 Ar Co-57
    Co-57 fluoride Ar Co-57 fluoride
    Co-57 Ar/oxygen Co-57 oxide
    Rb-83 Rb-83 bromide Ar Rb-83 bromide
    Rb-83 chloride Ar Rb-83 chloride
    Rb-83 iodide Ar Rb-83 iodide
    Sr-85 Sr-85 same as Sr-83
    Sr-85
    Sr-85
    Ti-44 Ti-44 Ar Ti-44
    Ti-44 Ar/Acetylene Ti-44 carbide
    Ti-44 Ar/Nitrogen Ti-44 nitride
    Ti-44 Ar/B2H6 Ti-44 boride
    Cr-51 Cr-51 Ar Cr-51
    Cr-51 Ar/Acetylene Cr-51 carbide
    Cr-51 Ar/H2S Cr-51 sulfide
  • [0197]
    [0197]
    TABLE 41
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    *Se-75 Se-72 same as Se-72
    Se-72
    Se-72
    Se-72
    Se-72
    Iridium
    Indium
    Thallium
    Zr-88 Zr-88 same as Zr-86
    Zr-88 diboride
    Zr-88
    Zr-88
    Zr-88
    Zr-88
    Zr-88
    Graphite
    Boron
    Zr-93 Zr-93 same as Zr-86
    Zr-93 diboride
    Zr-93
    Zr-93
    Zr-93
    Zr-93
    Zr-93
    Graphite
    Boron
  • [0198]
    [0198]
    TABLE 42
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    *Zr-95 Zr-95 same as Zr-86
    Zr-95 diboride
    Zr-95
    Zr-95
    Zr-95
    Zr-95
    Zr-95
    Graphite
    Boron
    La-138 La-138 Ar La-138
    La-138 Ar/Oxygen La-138 oxide
    La-138 Ar/B2H6 La-138 boride
    Boron Ar/La-138Cl3 La-138B6
    Gd-146 Gd-146 same as Gd-149
    Gd-146 iodide
    Nb-92 Nb-92 same as Nb-90
    Nb-92
    Nb-92
    Boron
    Graphite
    *Cd-109 Cd-109 fluoride same as Cd-115
    Cd-109
    Cd-109
    *Cd-115m Cd-115m same as Cd-115
    *In-114m In-114m same as In-115
  • [0199]
    [0199]
    TABLE 43
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    *Sn-119m Sn-119m same as Sn-123
    Sn-119m
    Sn-119m
    Tellurium
    *Sn-121m Sn-121m same as Sn-123
    Sn-121m
    Sn-121m
    Tellurium
  • [0200]
    [0200]
    TABLE 44
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Nb-93m Nb-93m same as Nb-90
    Nb-93
    Nb-93
    Boron
    Graphite
    Nb-94 Nb-94 same as Nb-90
    Nb-94
    Nb-94
    Boron
    Graphite
    Nb-95 Nb-95 same as Nb-90
    Nb-95
    Nb-95
    Boron
    Graphite
    *Mo-93 Mo-93 same as Mo-99
    Mo-93
    Graphite
    Graphite
    Sb-125 Sb-125 same as Sb-119
    Tellurium
    Indium
    *Sb-124 Sb-124 same as Sb-119
    Tellurium
    Indium
  • [0201]
    [0201]
    TABLE 45
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    *Te-129m Te-129m same as Te-132
    Te-129m
    Gallium
    Lead
    Indium
    *Ru-103 Ru-103 same as Ru-97
  • [0202]
    [0202]
    TABLE 46
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    I-129 CuI-129 same as I-125
    AgI-129
    KI-129
    Ti(I-129)2
    Zr(I-129)4
    Hf(I-129)4
    Cr(I-129)2
    Dy(I-129)3
    Er(I-129)3
    Eu(I-129)2
    Ho(I-129)3
    Li(I-129)
    Lu(I-129)3
    Nd(I-129)3
    Rb(I-129)
    Sm(I-129)2
    Tb(I-129)3
    Titanium
    Zirconium
    Hafnium
    Chromium
    Dysprosium
  • [0203]
    [0203]
    TABLE 47
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    I-129 Erbium same as I-125
    Europium
    Holmium
    Lithium
    Lutetium
    Neodymium
    Rubidium
    Samarium
    Terbium
    Cs-137 Cs-137 bromide same as Cs-129
    Cs-137 chloride
    Cs-137 fluoride
    Cs-137 iodide
  • [0204]
    [0204]
    TABLE 48
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Ce-144 Ce-144 same as Ce-134
    Ce-144 fluoride
    Ce-144
    Pm-143 Pm-143 Ar Pm-143
    Pm-145 Pm-145 same as Pm-143
    *Sm-145 Sm-145 same as Sm-153
    Sm-145 bromide
    Sm-145 fluoride
    Eu-155 Eu-155 Ar Eu-155
    Eu-155 fluoride Ar Eu-155 fluoride
    Gd-153 Gd-153 same as Gd-149
    Gd-153 iodide
    Dy-159 Dy-159 same as Dy-166
    Dy-159 bromide
    Dy-159 chloride
    Dy-159 fluoride
    *Tm-171 Tm-171 same as Tm-170
    Tm-171 bromide
    Tm-171 fluoride
    Tm-171
    *Sm-151 Sm-151 same as SM-153
    Sm-151 bromide
    Sm-151 fluoride
  • [0205]
    [0205]
    TABLE 49
    MANUFACTURING PARAMETERS FOR TEMPORARY
    REMOVABLE MULTILAYERED RADIOACTIVE
    MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    *Tb-160 Tb-160 same as Tb-155
    Tb-160 bromide
    Tb-160 fluoride
    Tb-160
  • [0206]
    [0206]
    TABLE 50
    MANUFACTURE FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Lu-173 Lu-173 Ar Lu-173
    Lu-173 Ar Lu-173
    fluoride fluoride
    Lu-174 Lu-174 same as Lu-173
    Lu-174
    fluoride
    Hf-172 Hf-172 same as Hf-170
    Hf-172
    Hf-172
    Hf-172
    Hf-175 Hf-175 same as Hf-170
    Hf-175
    Hf-175
    Hf-175
    *Hf-178m2 Hf-178m2 same as Hf-170
    Hf-178m2
    Hf-178m2
    Hf-178m2
  • [0207]
    [0207]
    TABLE 51
    MANUFACTURE FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Hf-179m2 Hf-179m2 same as Hf-170
    Hf-179m2
    Hf-179m2
    Hf-179m2
    *Hf-181 Hf-181 same as Hf-170
    Hf-181
    Hf-181
    Hf-181
    *Hf-182 Hf-182 same as Hf-170
    Hf-182
    Hf-182
    Hf-182
    *W-185 Hf-185 same as W-187
    Hf-185
    Hf-185
    Hf-185
    W-188 W-188 same as W-187
    W-188
    Re-183 Re-183 same as Re-181
    Os-194 Os-194 same as Os-191
  • [0208]
    [0208]
    TABLE 52
    MANUFACTURE FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    *Ir-192 Ir-192 same as Ir-189
    Ir-194m Ir-194m same as Ir-189
    *Hg-203 Hg-203 same as Hg-197
    fluoride
    Hg-203
    *Bi-210m Bi-210m same as Bi-210
    Bi-210m
    Tellurium
    Am-241 Am-241 Ar Am-241
    Am-242m Am-242m same as Am-241
    *Am-243 Am-243 same as Am-241
    Cm-243 Cm-243 Ar Cm-243
    Cm-245 Cm-245 same as Cm-243
    U-233 U-233 same as U-231
    U-233
    Boron
    U-234 U-234 same as U-231
    U-234
    Boron
  • [0209]
    [0209]
    TABLE 53
    MANUFACTURE FOR TEMPORARY REMOVABLE
    MULTILAYERED RADIOACTIVE MICROSPHERES
    (Energy greater than 100 KeV and Half-Life
    greater than 15 days, or Energy less than 100 KeV
    and Half-Life greater than 130 days)
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    U-235 U-235 same as U-231
    U-235
    Boron
    U-236 U-236 same as U-231
    U-236
    Boron
    *U-238 U-238 same as U-231
    U-238
    Boron
  • [0210]
    [0210]
    TABLE 54
    MANUFACTURE FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Si-32 Si-32 Ar Si-32
    Si-32 Ar/Acetylene Si-32 carbide
    Si-32 Ar/Oxygen Si-32 oxide
    Graphite Ar/Si-32H4 NiSi-32
    P-32 Platinum (P-32)2 Ar Platinum
    phosphide-32
    Platinum Ar/H3P-32 Platinum
    (P-32)2
    P-33 Platinum(P-33)2 same as P-32
    Platinum
    Cl-36 Neodymium (Cl-36)3 Ar Neodymium
    chloride-36
    Holmium (Cl-36)3 Ar Holmium
    chloride-36
    K-40 K-40 chloride Ar K-40 chloride
    K-40 iodide Ar K-40 iodide
    K-42 K-42 chloride same as K-40
    K-42 iodide
    Ca-45 Ca-45 Ar Ca-45
    Ca-45 fluoride Ar Ca-45 fluoride
    Ca-45 Ar/Acetylene Ca-45 carbide
    S-35 Vanadium Ar/H2S-35 VS-35
    Tungsten Ar/H2S-35 W(S-35)z
  • [0211]
    [0211]
    TABLE 55
    MANUFACTURE FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Ti-45 Ti-45 same as Ti-44
    Ti-45
    Ti-45
    Ti-45
    Bi-210 Bi-210 Ar Bi-210
    Bi-210 Ar/Oxygen Bi-210 oxide
    Tellurium H3Bi (BI-210)2Te3
    Sr-89 Sr-89 same as Sr-83
    Sr-89
    Sr-89
    Sr-90 Sr-90 same as Sr-83
    Sr-90
    Sr-90
    Y-90 Y-90 same as Y-87
    Y-90 chloride
    Zr-89 Zr-89 same as Zr-86
    Zr-89 diboride
    Zr-89
    Zr-89
    Zr-89
    Zr-89
    Zr-89
    Graphite
    Boron
  • [0212]
    [0212]
    TABLE 56
    MANUFACTURE FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Pd-112 Pd-112 same as Pd-100
    Ag-111 see Ag-111 previous
    entry
    Cd-113m Cd-113m fluoride same as Cd-115
    Cd-113m
    Cd-113m
    Cd-115m Cd-115m fluoride same as Cd-115
    Cd-115m
    Cd-115m
    In-115 In-115 Ar In-115
    Sn-123 Sn-123 Ar Sn-123
    Sn-123 Ar/Oxygen Sn-123 oxide
    Sn-123 Ar/Hydrogen sulfide Sn-123 sulfide
    Tellurium Ar/Sn-123H4
    Cs-135 Cs-135 bromide same as Cs-129
    Cs-135 chloride
    Cs-135 fluoride
    Cs-135 iodide
    Pr-143 see previous Pr-143
    entry
    Ho-166 see previous Ho-166
    entry
  • [0213]
    [0213]
    TABLE 57
    MANUFACTURE FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Tm-170 see previous Tm-170
    entry
    Yb-175 see previous Yb-175
    entry
    Lu-177 Lu-177 same as Lu-173
    Lu-177 fluoride
    W-185 W-185 same as W-187
    W-185
    W-187
    Boron
    Graphite
    W-188 W-188 same as W-187
    W-188
    W-188
    Boron
    Graphite
    *Tl-204 Tl-204 same as Tl-201
    Vanadium
    Th-231 Th-231 same as Th-231
    Th-231 hexaboride
    Th-231
    Th-231
    Th-231
    Th-231
  • [0214]
    [0214]
    TABLE 58
    MANUFACTURE FOR ELECTRON-PRODUCING
    MULTILAYERED RADIOACTIVE MICROSPHERES
    High Energy Electron Particle Radiation
    without Major Gamma-ray Component
    TARGET ATMOSPHERE
    RADIONUC MATERIAL GAS COAT
    Th-234 Th-234 same as Th-231
    Th-234 hexaboride
    Th-234
    Th-234
    Th-234
    Th-234
  • [0215]
    In one embodiment, pure metal is deposited onto microspherical substrates from plasma in an atmosphere containing only an inert gas and a radiation-emitting chemical compound is deposited onto microspherical substrates when a radiation-emitting reactive gas such as a radioactive hydride gas is introduced into the system to form a radioactive compound from the metal and gas. In another embodiment, cycles of different coating materials are alternated to produce a laminate of thin hard (high boiling point metal) and soft (radiation-emitting compound) coats such as for example of the materials described above. Using adequate biasing of the substrate, each cycle is approximately thirty seconds in duration so that one layer of radiation-emitting compound is sealed by one layer of pure (high boiling point) metal each sixty seconds.
  • [0216]
    Depending on the materials being coated and the efficiency of the deposition apparatus, each alternate layer is approximately 100 Angstroms to 1000 Angstroms thick, depending on the coating method used as well as the apparatus and atomic weights of the elements being coated. The coating of the soft radiation-emitting layer with a hard-metal layer seals the radiation-emitting layer before it begins to break or vacuum weld with other microspheres. This is continued using one of the coating methods outlined hereinafter until the desired activity or radiation-emitting compound is accumulated on the microsphere. A laminate of thin hard (metal nitride, metal oxide, metal carbide, or metal carbonitride) and soft (metal-radionuclide compound) coats are produced.
  • [0217]
    The outer layers 18 and 20 confine the radiation-emitting layer 16. In one embodiment, these layers are made of a material that permits the transmission of electrons through them such as carbon thus permitting electron seeds by the appropriate selection of the material for the layer 16 but in other embodiments are made of metals that are hard and protective but absorb or filter electron particles. These materials in layers 18 and 20 are included in embodiments with radiation-emitting materials in the layer 16 to protect, seal, identify and under some circumstances provide filtering of radiation.
  • [0218]
    In some embodiments, the layer 18 is a diffusion barrier that prevents the movement of radioactivity outwardly toward the surface of the microsphere 10. The outer layer may serve as both diffusion barrier and provide mechanical protection or color identification if desired. The material of the diffusion barrier is selected for its functions in conjunction with the nature of the material that provides the radiation.
  • [0219]
    Suitable diffusion barriers include: (1) single metals such as gold, palladium, tantalum, tungsten, platinum, and titanium; or (2) multilayered combinations of metals such as gold-palladium-titanium, gold-titanium and tungsten-titanium; or (3) compounds such as titanium nitride (TiN), and titanium carbide (TiC), tungsten carbide (WC), tungsten nitride (WN), tungsten-titanium nitride (TiWN), hafnium nitride (HfN), hafnium carbide (HfC), zirconium nitride (ZrN), zirconium carbide (ZrC), vanadium carbide (VC), boron carbide (BC) and tungsten boride (WB); or (4) nonmetallic elements or compounds such as diamond or diamond-like carbon.
  • [0220]
    The preferred diffusion barrier materials of the present invention are titanium nitride, tungsten carbide, hafnium nitride and groups of layers such as a titanium layer 100 nm (nanometers) thick, a layer of palladium 100 nm thick, and a layer of gold 300 nm thick. The purpose of the diffusion barrier is to prevent diffusion of the radiation-emitting component into the outer coats of the multilayer radiation-emitting microsphere. It also serves as a radiation-emitting gas barrier for radionuclides which sublimate or form gases at room temperature.
  • [0221]
    An essential criterion of thin film structures is that they maintain structural integrity. Pronounced reaction or interdiffusion of thin films is known to occur over short distances of several hundred angstroms. Thin metal layers tend to diffuse and react chemically, and this tendency is enhanced by thin film defects or grain boundaries. The diffusion barrier helps prevent this diffusion.
  • [0222]
    It is important to prevent radiation-emitting materials from diffusing through the outer metal coats of the multilayer radiation-emitting microsphere because metals such as I-125 can sublimate into a gas upon exposure to air, or if they are implanted into a patient, the I-125 can enter the bloodstream and become concentrated in the thyroid gland. Diffusion barriers are not necessary when the radionuclide element is a chemically stable or high boiling point metal or metal compound that is relatively inert.
  • [0223]
    To further reduce leakage of radioactive material, a layer of metal that chemically reacts with the material in the radioactive layer may be sputtered or otherwise coated over the radioactive material as a chemical diffusion layer before the mechanical diffusion layer. This layer reacts with the radioactive material and seals the mechanical diffusion layer. For example, silver may be sputtered as an even coat over the radioactive iodide layers to reduce leakage. Moreover, the density of the diffusion layer and its uniformity is maximized, such as by coating the diffusion layer on using the lowest possible pressure and introducing as much energy as feasible while avoiding welding of microspheres, such as by the introduction of a magnetic field and heat during the coating process.
  • [0224]
    The outer coat 20 is a thick spherical (up to 0.10 mm) protective coat containing the inner coats 16 and 18. The spherical thick protective coat may be composed of: (1) a resistant human tissue-compatible metal which also has low atomic weight to minimize X-ray shielding such as titanium or other corrosion-resistant metal alloy such as stainless steel; or(2) a resistant human tissue-compatible metal compound (using reactive acetylene nitrogen, oxygen, methane, or carbon monoxide gases during coating to form carbides, nitrides, or carbonitrides of transition metals or other metals) such as titanium carbide, titanium nitride, titanium carbonitride, titanium aluminum nitride, zirconium nitride and hafnium nitride; or (3) a resistant human tissue-compatible metal coat less than 0.1 millimeters thick which has a high atomic weight such as tantalum, platinum or gold; or (4) a human tissue-incompatible metal coat which is covered by a tissue-compatible thin coat.
  • [0225]
    If a tissue-compatible outermost coat such as sputtered diamond, tantalum, or titanium is applied over the thick protective metal casing, then the more toxic but low atomic weight metals such as beryllium, vanadium, nickel and boron nitride may be used as the thick casing. Appropriate outermost coat are typically thin and consist of a special-purpose coat designed to enhance physical properties of the seed such as diamond or diamond-like carbon, platinum, or tantalum. These coats individually enhance the multilayer radiation-emitting microsphere by adding hardness, and corrosion resistance. The outermost thin coat may also be used to produce different seed identification colors.
  • [0226]
    To produce color, the outermost thin coat may include of titanium nitride (TiN) to produce a golden color, titanium carbonitride (TiCN) to produce a brown color, titanium aluminum nitride (TiAlN) to produce a black color, titanium carbide (TiC) to produce a gray color, zirconium nitride (ZrN) to produce a silver-yellow color, and hafnium nitride (HfN) to produce a yellow-green color.
  • [0227]
    Some appropriate strong hard corrosion-resistant human tissue-compatible metal include titanium, hafnium, and zirconium. Low atomic weight metal alloys such as stainless steel are also satisfactory. Other usable corrosion-resistant metals include tantalum, tungsten, gold, and platinum. Because this “thick” layer is still relatively thin (less than 0.1 mm) and because the coat is highly uniform and spherical, a high atomic weight metal such as platinum or gold may still be effectively used as the thick protective coat without causing radiation aniostropy and with minimal gamma-ray shielding and loss of radioactivity.
  • [0228]
    Because of spherical uniform construction, any self-shielding can be compensated for by increasing the seed activity. In the preferred embodiment of this invention, metals having low atomic weight with minimal shielding of low-energy gamma rays, tissue and corrosion resistance, high hardness and high boiling point are preferred for the casing of multilayer radiation-emitting microsphere's containing low energy emitting (less than 100 KeV) radionuclides. Titanium is such a metal. The preferred metal for casings of multilayer radiation-emitting microsphere's containing high energy emitting (greater than 100 KeV) radionuclides have high atomic weight with some shielding of low energy gamma rays and very little shielding of high energy gamma rays, high tissue and corrosion resistance, high hardness and very high boiling point. Two such metals are tantalum and tungsten.
  • [0229]
    The casing 20 also may include a strong hard corrosion-resistant human tissue-compatible non-metallic element. The preferred non-metallic thick protective coat is sputtered or plasma-deposited diamond or plasma-deposited diamond-like carbon. These non-metallic coats not only have the advantage of low atomic weight to minimize X-ray self-shielding of the radionuclide layer, but they also have the advantage of being completely non-ferromagnetic.
  • [0230]
    Other hard corrosion-resistant metals include carbides, metal nitrides, metal borides, metal oxides, metal sulfides, or metal carbonitrides. The preferred metallic compound thick protective coats of the present invention include titanium carbide, titanium nitride, titanium carbonitride, tantalum carbide, tungsten carbide, hafnium nitride, and zirconium nitride.
  • [0231]
    All of these thick coats may be incorporated individually into different seed designs to adequately serve as a hard crush-resistant corrosion-resistant protective outer casing of the multilayer radiation-emitting microsphere. All of these coats may be easily applied by the standard deposition or reactive deposition techniques described elsewhere.
  • [0232]
    Additionally, if a tissue-compatible outermost coat such as sputtered diamond, tantalum, or titanium is applied over the thick protective metal casing, then the thick protective layer need not be composed of a tissue-compatible material. In this case, more toxic but low atomic weight metals such as beryllium, vanadium, nickel and boron nitride may be used as the thick protective casing.
  • [0233]
    In FIGS. 2-5, there are shown four other embodiments of radiation-emitting microspheres 10A, 10B, 10C and 10D respectively having corresponding layer sections 14A-14D with different numbers of and/or thicknesses of its layers or coats, ranging from four coats to five coats but normally with one thick protective coat and several thin coats so as to minimize the diameter of the radiation-emitting microsphere. The microsphere 10A of FIG. 2 has a hollow substrate 12A but would include a solid spherical substrate instead. For convenience the coats are numbered from the center outwardly regardless of their specific composition or use. The extra layers are an optional special-purpose inner spherical coat designed to enhance diagnositc X-ray or magnetic resonance or PET imaging and an optional thin outermost special-purpose coat.
  • [0234]
    The optional thin (less than 0.01 mm thick) outermost special-purpose coat is shown at 22C in FIG. 4 and at 24D in FIG. 5. This optional outer coat may be dc, rf, laser ablation or magnetron sputtered, ion-plated, ion-beam sputtered, orcurvilinearor standard cathodic arc plasma deposited materials such as diamond, diamond-like carbon, titanium nitride, titanium carbonitride, titanium carbide, tantalum carbide, hafnium nitride, zirconium nitride, platinum, or tantalum. These coats individually produce additional desirable multilayer radiation-emitting microsphere physical characteristics such as increased hardness, scratch resistance, colors used for identification, reduced friction, increased tissue compatibility, and increased corrosion resistance that enhance the basic spherical sputtered laminated multilayer radiation-emitting microsphere design of the present invention.
  • [0235]
    Optional thin outer multilayer radiation-emitting microsphere coats may be used to produce different seed identification colors to clearly label seeds of differing compositions or to differentiate seeds with low versus high activities, long versus short half-lives, or low versus high gamma energies. These layers must not only produce colors but they must also be tissue compatible and corrosion resistant, because they are the outermost layer of the multilayer radiation-emitting microsphere.
  • [0236]
    Diamond coated multilayer radiation-emitting microsphere's are less likely to be damaged by surgical instrumentation. Also, reduced friction of this surface coat makes the multilayer radiation-emitting microsphere of the present invention less likely to jam in an autofeeding tissue implantation gun. A thin layer of diamond (less than 0.001 mm) thick produced by reactive cathodic arc deposition from a carbon-containing gas is a preferred optional thin outer multilayer radiation-emitting microsphere coat of the present invention.
  • [0237]
    If necessary, to reduce porosity or remove crystallization of the coats of the finished product, or to improve adhesion between layers, after completion of coat, the multilayer radiation-emitting microsphere's may be annealed in a separate apparatus. In some embodiments, this may be done by heating close to the bulk metal melting temperature in a microsphere bouncing pan and thus result in a fine crystal structure typical of annealed materials.
  • [0238]
    The optional inner spherical uniform special purpose coats may be used to enhance imaging of the multilayer radiation-emitting microsphere by conventional radiographs, computed tomography or magnetic resonance imaging or other remote imaging arrangements. It may be a relatively thin (less than 0.01 mm thick) rf, magnetron, laser ablation or dc sputter-deposited, or ion-plated, or ion-beam self-sputtered, curvilinear cathodic arc plasma deposited or standard cathodic arc plasma deposited layer for diagnostic X-ray imaging enhancement or magnetic resonance imaging enhancement or positron emission imaging enhancement (PET) or single position emission computed topography (SPECT) for seed identification.
  • [0239]
    A coat such as gadolinium, erbium, terbium, thulium, cerium, cobalt fluoride, dysprosium oxide, dysprosium sulfide, neodymium fluoride, terbium oxide, samarium bromide, thulium oxide, etc. is chosen for the purpose of magnetic resonance imaging because of their properties of paramagnetism and high magnetic susceptibility as well as high-boiling point that reduces vacuum welding during coat deposition.
  • [0240]
    Elements or compounds that are suitable for the magnetic resonance imaging layer of the present invention include cerium (B.P. 3,468 C, magnetic susceptibility (ms) in 10−6 cgs [ms] +5,160.0), cobalt fluoride (B.P. 1,400 C, ms +9,490.0), dysprosium oxide (M.P. 2,340 C, ms +89,600.0), dysprosium sulfide (M.P. - - - , ms +95,200.0), erbium (B.P. 2,900 C, ms +44,300.0) gadolinium (B.P. 3,000 C, ms +75,000.0), manganese dichloride (B.P. 1,900 C, ms +14,300.0), neodymium fluoride (B.P. 2,300, ms +4,980.0), samarium bromide (B.P. 1,880, +5,337.0), terbium (B.P. 2,800 C, ms +146,000.0), terbium oxide (B.P. - - - , ms +78,340.0), thulium (B.P. 1,727 C, ms +25,000.0), thulium oxide (B.P. - - - ms +51,444.0).
  • [0241]
    Because these elements have sufficiently high boiling points to be effectively coated onto the multilayer radiation-emitting microsphere of the present invention, and because they have significantly different magnetic susceptibilities, it is possible to separately identify different multilayer radiation-emitting microsphere's coated with different magnetic resonance imaging agents within the same tumor for purposes of tumor dose calculations. This is significant because, to take full advantage of the wide variety of multilayer radiation-emitting microsphere's of the present invention, it is advantageous to implant more than one type of multilayer radiation-emitting microsphere in one procedure into the same tumor.
  • [0242]
    To be discharged from a hospital, a patient with permanently-implanted radiation-emitting seeds must wait until the total activity of the seeds falls below a permissible level specified for that particular radionuclide. Using short-lived radionuclides, these radiation-emitting activity levels can be obtained within a reasonable number of days, thus avoiding excessively long hospitalization, while still delivering adequate tumor dose.
  • [0243]
    The central sphere or other coats may be formed of a material that is heatable by remotely radiated energy for hyperthermia and/or a magnetic material that enables force to be applied to the seed to move it around using externally radiated energy to avoid damage to tissue. For example, ferromagnetic materials may be used that are heated by induced radio frequency energy to the Curie temperature and have a Curie temperature appropriate for hyperthermia such as, for example, 50 degrees Centigrade. Moreover, a strongly magnetic material may cause movement of the seed by externally applied electromagnetic fields.
  • [0244]
    Substrate cores composed of a suitable ferromagnetic alloy or paramagnetic or ferroelectric compounds in the form of microspheres that have a sharp Curie transition in the range of 40 to 50 degrees Centigrade may be manufactured in situ by coating a starting seed with a ferromagnetic compound such as by sputtering, laser ablation or cathodic arc deposition using the appropriate target materials and/or reactive gases or by making the entire seed of the appropriate material. Elements suitable for Curie-transition-point substrate microspheres for use in the present invention include iron, cobalt, nickel, dysprosium and gadolinium. Other alloys can be formed to have the proper Curie point.
  • [0245]
    Elements and compounds are combined in optimal proportions to produce a final seed that has a sharp Curie transition point in the range of 42 degrees Centigrade to 50 degrees Centigrade. The compounds and elements may be alloyed in situ by sputtering from the appropriate shuttered targets. Differential shuttering of the targets permits control of the sputtering rate of each target, and permits precise control of the percentages and proportions of target materials alloyed onto the substrate microspheres. Similarly, the proportions can be easily controlled using laser ablation techniques, wherein a laser is used to vaporize one or several sputtered targets.
  • [0246]
    For example, the nickel series of alloys can be used to produce microspherical substrates with Curie transition points in the range of 42 to 50 degrees Centigrade. These include: Vanadium 4%+Nickel 96%; Molybdenum 6%+Nickel 94%; Chromium 8%+Nickel 92%; Titanium 9%+Nickel 91%; Sb 7%+Nickel 93%; Silicon 8% +Nickel 92%; Aluminum 12%+Nickel 88%; Platinum 28%+Nickel 72%; Manganese 17%+Nickel 83%; Copper 29%+Nickel 71%.
  • [0247]
    Although the embodiments of FIGS. 1-5 show from three to five coats, a seed may be formed of a 0.20 mm diameter tantalum center, a 0.01 mm to 0.045 thick Ti (I-125)2/TiN inner coat and a 0.05 mm thick titanium nitride outer coat. This structure is possible because the TiN serves as both a diffusion barrier and as a protective coat, thus removing the need for another diffusion barrier coat.
  • [0248]
    Radiation hazards can be reduced by utilizing a coat of non-radioactive material instead of a radioactive layer, which non-radioactive material is either naturally occurring or isotopically enhanced material that is one neutron away from being a stable radioactive isotope. This material may then be activated by neutron radiation just before being used to avoid forming seeds with higher radioactivity than needed and permitting them to decay until used. The material should have a thickness range of 25 microns to 50 microns (0.025 mm to 0.050 mm) when the starting material is a non-enriched natural element that is converted to the corresponding radioactive isotopes by thermal neutron bombardment. The amount of material is related to the amount of radioactivity that can be produced by neutron eradiation of the element.
  • [0249]
    In use, the multilayer radioactive microspheres are surgically implanted, either permanently by placing them directly into the tissue, or temporarily by placing them in catheters, or removable tubes, etc. One surgical technique for implantation of multilayer radioactive microspheres includes selecting the half-life, energy, activity and field strength of the implant in accordance with the time of implantation, implanting the high energy microspheres and removing high energy microspheres after a time period long enough to destroy only neoplastic tissue and not long enough for the destruction of differentiated healthy cells in accordance with the intensity of the radiation. However, if the high energy microsphere has a relatively short half-life, it need not be removed and may be permanently implanted. Also, low-energy miscrospheres are not hazardous to others because the energy is almost completely absorbed within the patient. Thus, low-energy microspheres are usually permanently implanted, unless a high dose rate is desired. Even for temporary implants, low-energy implants are less hazardous to hospital personnel.
  • [0250]
    A plurality of low energy microspheres may be implanted at distances from each other in accordance with the intensity wherein only neoplastic tissue is destroyed by physically confining the major radiation dose to the neoplastic tissue by virtue of the physical characteristics of the microspheres. An auto-feeding implantation gun may be used.
  • [0251]
    In one form of treatment, between 30 and 300 low activity multilayer radioactive microspheres are implanted permanently into a human tumor at approximately 1 centimeter intervals throughout the volume wherein continuous-low-dose rate low energy irradiation is produced at less than 1.5 Gray per hour. In conjunction with the implant, minimum doses of 80 to 3,000 Gray to the tumor volume over the average lifetime of the multilayer radioactive microsphere may be delivered.
  • [0252]
    The idea of synchronizing cells prior to radiation therapy has been tried clinically by utilizing chemotherapy agents as cell synchronizing agents. For example, hydroxyurea has been tried as a cell synchronizing chemical agent prior to external beam irradiation in the treatment of cervical cancer and malignant glioblastomas of the brain. These trials have been only moderately successful or unsuccessful.
  • [0253]
    An “inverse dose-rate effect” has been described in which decreasing the dose rate of radiation delivery results in increased cell killing. This paradoxic effect has been explained by the fact that at certain dose rates, cells tend to progress through the cell cycle and become arrested in G-2 or G-2/S, a very radiosensitive phase of the cell cycle. Further continuous low-dose rate irradiation of these “arrested and radiosensitized” cells then results in very effective cell killing, far beyond that expected from the relatively low radiation doses delivered.
  • [0254]
    The actual dose-rates that produce this effect vary widely for different cell lines. The dose-rates that effectively produce a G-2 block for a given tumor type can be determined experimentally by culturing tumor cells and analyzing the cell-cycles using standard flow-cytometry techniques. It can also be determined by trial and error with a patient. It has been determined by one investigator that the minimum dose-rate necessary to stop cell division of HeLa cells was approximately 23 rad/hour, but it was approximately 270 rad/hour for V-79 cells—a ten-fold difference.
  • [0255]
    For these “optimum” dose rates that stopped cell division, all the cells were noted to progress through G-1 and S-phase, with a small delay in S-phase, followed by complete block in G-2 phase. HeLa cells showed a dramatic effect of redistribution of cells into sensitive phases of the cell cycle during exposure, which was reflected in the survival curves at low dose rate, and more cell killing per unit dose was observed at 37 rad/hour than at 74 rad/hour. Thus, at the optimal dose rate, cells tend to progress through the cell cycle and become arrested in G-2, a known radiosensitive phase of the cell cycle. While so arrested, they may be more efficiently killed by delivery of further radiation. At higher dose rates, cells are “frozen” in the phase of the cycle they are in at the start of irradiation. At lower-than-optimal dose rates, the cells escape the G-2 block and proceed to cycle and divide as usual during irradiation.
  • [0256]
    Each tumor-type has a characteristic “optimal-dose rate” that produces prolonged cell cycle arrest in the radiosensitive G-2 phase. This “optimal-dose-rate” can be determined using standard cell culture and cell-cycle analytic techniques. Bedford and Mitchell noted that dose rates of 38 rads per hour for HeLa cells and 90 rads per hour for V-79 Chinese hamster cells essentially prevented cell division, but such continuous irradiation had no effect upon the progress of cells through G-1 or S-phase, but produced a G-2 delay and prevented cell division.
  • [0257]
    The multilayer radioactive microspheres disclosed in the present invention can be matched (by producing multilayer radioactive microspheres with specifically matched energies, half-lives, and activities) to a particular tumor to produce this “optimal-dose-rate” throughout the tumor target volume, and cause a prolonged block at G-2, and thus serve as a “radiosensitizer” if present during administration of a conventional course of external-beam irradiation. In other words, the multilayer radioactive microspheres disclosed in the present invention can be manufactured to “match” the radiobiology of a particular tumor and thus produce an “optimal” dose rate of continuous irradiation and thus serve as a “radiosensitizer” by blocking the cells within the tumor target volume in the G-2 phase of their cell cycles.
  • [0258]
    Percutaneous needle biopsy using either CT (computed tomography) or sonographic (ultrasound) guidance is a common procedure that has been developed over the past 15 years. In the early years of radiologically guided needle biopsy, most biopsies were performed using thin-caliber (21-gauge to 22 gauge) needles which provided a known wide margin of safety. The use of thin-gauge needles to perform biopsies is historically associated with the lowest risk of bleeding and tissue trauma. Even overlying loops of stomach or small intestine are not a contraindication to needle biopsy if small- caliber thin-gauge needles are used. The most common human body sites in which radiologically guided biopsy has been performed include the liver, pancreas, retroperitoneum, adrenal gland, pelvis, chest, bone, extremity, and neck.
  • [0259]
    Because of its small size, (usually less than 0.40 mm diameter) the multilayer radioactive microspheres of the present invention can be easily and safely implanted into almost any body site using a small-caliber thin-gauge (21 G to 22 G) interstitial implantation needle using the same techniques initially developed to perform percutaneous needle biopsies under CT and sonographic guidance. Additionally, multilayer radioactive microspheres of the present invention can be implanted using MRI guidance (magnetic resonance imaging).
  • [0260]
    The relatively recent use of computers to digitize the relative spatial coordinates of human body organs derived from CT, MRI, and PET (positron emission tomography) scans and produce three-dimensional images (Scandiplan, Scanditronix Inc, Uppsula, Sweden) could be utilized to stereotactically implant multilayer radioactive microspheres into specific body sites using such digitized data to guide the interstitial needle to specific Cartesian or polar body coordinates in relation to a reference system. While stereotactic frames have been used extensively in the past to perform neurosurgical procedures, stereotactic techniques have not been used in the past to implant radioactive seeds into body sites other than the brain, pituitary, or skull base. However, such stereotactic techniques may be applied to implant multilayer radioactive microspheres into any body site in a “stereotactic body-implantation” system using either a “stereotactic frame” or a “robotic-arm”.
  • [0261]
    Stereotactic brain surgery is a technique for guiding the tip of a probe into the brain through a hole drilled in the skull without having direct visualization of the surgical site. Such techniques have been developed and applied in the field of neurosurgery. Stereotactic surgical frames have been coupled with CT scanners since any point identifiable on a CT scan can be related to stereotactic coordinates, allowing stereotactic guidance of surgical instruments for biopsy or neurosurgical procedures. There are numerous geometrical systems upon which stereotactic frame coordinates could be based.
  • [0262]
    The four main types of frames developed to date include: (1) polar coordinate; (2) arc-radius; (3) focal point; (4) phantom target. A typical polar coordinate stereotactic system requires that a trajectory is described in polar coordinates relative to an entry point. Arc radius frames employ a probe in a semicircular arc which is introduced orthogonal to a tangent along the arc. Phantom or “dummy” devices may use any coordinate system to determine the angles and probe lengths of a stereotactic device mechanically rather than trigonometrically. This approach may be used to implant microspheres at the selected locations.
  • [0263]
    A new technique in which a commercially available robot (Unimation Puma 200 robot) performs a “robotic stereotactic” brain biopsy is known. Spatial information determined by CT scanning is tied into a base frame used to immobilize the patient, and this information is translated into robotic spatial coordinates that are used to direct the robotic arm and biopsy needle to the proper location.
  • [0264]
    Robotic stereotactic techniques may be applied to implant multilayer radioactive microspheres into any body site in a “robotic body-implantation” system without relying upon a “stereotactic-frame”. The primary use of multilayer radioactive microspheres and related products is the safe delivery of high tumoricidal radiation doses to human tumors that are two to five times higher than those achievable by conventional external-beam radiation therapy. A second use of multilayer radioactive microspheres is the clinical use of multilayer radioactive microspheres as radiation sensitizers to enhance the tumor-effect of a conventional course of external-beam radiation therapy.
  • [0265]
    Generally, the primary use of multilayer radioactive microspheres is to permit safe delivery of tumoricidal doses of radiation that are two to five times higher than that deliverable by external means. In the first application of multilayer radioactive microspheres, the total dose delivered is the critical factor, and this dose must be completely tumoricidal. The second use of multilayer radioactive microspheres of the present invention includes the use of multilayer radioactive microspheres radiation as a radiation sensitizer in the sense that continuous low dose rate irradiation produced by multilayer radioactive microspheres optimally synchronizes tumors and causes cells to remain blocked in the radiosensitive portion of their cell cycles. In this secondary application, the dose of radiation delivered by the seed is not critical, and in most cases it may not even be substantially tumoricidal. However, the tumor volume dose rate is critical, and it must be high enough to hold cells in the G-2 block 24 hours per day, but it must be low enough to permit cells to progress through their cell cycles until they come to G-2. An excessively high dose rate would result in immobilization of all cells at their particular points within their cell cycles and is an undesirable effect.
  • [0266]
    Because of their small diameters, the multilayer radioactive microspheres of the present invention may be implanted using thin-caliber 21-Gauge or 22-Gauge needles using either CT, MRI, or sonographic guidance techniques originally developed in the field of radiology to perform percutaneous needle biopsies.
  • [0267]
    Stereotactic techniques developed and applied to the field of neurosurgery are now applied to all body sites to permit stereotactic implantation of multilayer radioactive microspheres of the present invention into any body site. A stereotactic body frame is introduced for implantation of multilayer radioactive microspheres using CT or MRI guidance.
  • [0268]
    Robotic techniques developed and applied to the field of neurosurgery are now applied to all body sites to permit robotic implantation of multilayer radioactive microspheres of the present invention into any body site. A robotic multilayer radioactive microspheres implantation system is introduced for implantation of multilayer radioactive microspheres using CT or MRI guidance coupled to a robotic arm without a stereotactic frame.
  • [0269]
    Multilayer radioactive microspheres implanted into human tumor tissues whether permanently or temporarily, are used to deliver tumoricidal radiation doses that are two to five times higher than those achievable using conventional external-beam radiation therapy techniques. In some cases, a standard course of radiation therapy may be delivered before seed implantation (4,000 cGy to 7,000 cGy in four to eight weeks) to achieve some tumor shrinkage prior to multilayer radioactive microsphere implantation. The combination of external-beam radiation therapy delivered either before or after seed implantation generally improves the homogeneity of the radiation within the target volume over that obtained using radioactive seeds alone.
  • [0270]
    External beam radiation therapy given before or after seed implantation is frequently used to irradiate occult microscopic metastases in regional nodes around a primary tumor and beyond the tumor target volume treated by the radioactive (multilayer radioactive microspheres) seed implant. For example, the treatment of a poorly-differentiated adenocarcinoma of the prostate could involve irradiation of the pelvic lymph nodes followed by radioactive seed (multilayer radioactive microspheres) implantation of the primary tumor mass.
  • [0271]
    This approach is effective because it is known that 5,000 cGy will control 90 percent of occult microscopic metastases in regional lymph nodes, but much higher doses of 16,000 cGy are necessary to achieve 90 percent control of a primary solid tumor mass in the prostate. Thus, sterilization of occult regional nodal metastases is accomplished by administration of external-beam radiation therapy, and sterilization of the primary tumor mass is accomplished by delivery of a high localized radiation dose using multilayer radioactive microspheres radioactive seed implantation of the tumor mass.
  • [0272]
    The course of external beam radiation therapy is then followed by implantation of multilayer radioactive microspheres radioactive seeds to safely deliver a high tumoricidal radiation dose to the target volume encompassing the tumor (8,000 cGy to 300,000 cGy). Alternatively, seed implantation alone can be used to treat a human tumor without the addition of external beam radiation therapy. Thus, tumoricidal radiation doses are achieved using either implantation of multilayer radioactive microspheres alone, or by administration of external beam radiation therapy before or after radioactive seed (multilayer radioactive microspheres) implantation. The critical point is that the primary goal of treatment using multilayer radioactive microspheres implantation with or without the addition of external beam radiation therapy is to achieve safe delivery of high tumoricidal radiation doses that are effective in controlling human tumors.
  • [0273]
    The primary types of endocurietherapy applications utilizing multilayer radioactive microspheres include: (1) permanent implantation of multilayer radioactive microspheres into human tumor tissues in locations such as the brain, pituitary, skull base, parotid, base of tongue, thyroid, tonsil, pharyngeal wall, neck nodes, mediastinum, spinal cord, lung, chest wall, axilla, brachial plexus, pleura, pancreas, liver, stomach, adrenals, abdominal wall, prostate, bladder, sacral tumors (chordoma), pelvic tumors (cervix, endometrium, prostate, bladder, rectum, anus, ovary, sarcomas), extremity tumors, et cetera, and implantation of multilayer radioactive microspheres surgical fabric in a resected tumor bed; (2) temporary interstitial needle or catheter implantation of multilayer radioactive microspheres (via removable tubes or sutures threaded through the needles, or via removable multilayered radioactive needles) into human tumor tissues located in accessible body sites such as the brain, floor of the mouth, anterior tongue, tonsil, face, scalp, skin surface, buccal mucosa, lip, extremities, neck nodes, chest wall, mediastinum, lung, bladder, cervix, endometrium, vagina, anus, rectum; (3) temporary intracavitary application of encapsulated multilayer radioactive microspheres or coated intracavitary cylinders or wires into accessible body cavities such as the bladder, rectum, vagina, cervix, endometrium, esophagus, trachea, bronchus, nose, nasopharynx et cetera; and (4) temporary application of multilayered radioactive plaques to accessible sites such as the hard palate, extremities, and globe of the eye.
  • [0274]
    In the second application, the dose delivered by the multilayer radioactive microspheres may be much less than tumoricidal. The goal of multilayer radioactive microspheres implantation in this case is not to directly kill the tumor by radiation emitted by the multilayer radioactive microspheres. Instead, the multilayer radioactive microspheres functioning as a radiation sensitizer is used to deliver continuous low dose rate radiation at a dose rate that serves to synchronize and block tumor cell populations in the most radio-sensitive phases of their cell cycles throughout a six to eight-week course of conventional external-beam radiation therapy.
  • [0275]
    This therapy accomplished by delivering radiation to the tumor tissues continuously 24-hours per day at a rate that permits cells to cycle yet causes the cell cycle to be blocked in the radio-sensitive part of the cell cycle (G2M, late G2, or G2/S). The continuous radiation dose rate must be sufficiently high to prevent cell escape from the block and thus hold them at the block, but it must be sufficiently low to permit cells to proceed through their cell cycles without complete cycle inhibition. If the cells are blocked and held in the most radiosensitive phases of their cell cycles, then the daily administration of conventional fractionated external-beam radiotherapy (given daily, 5 days/week, 1 fraction/day, 150-225 cGy/fraction, 100-400 cGy/minute dose rate) will be much more efficient in killing tumor cells that might otherwise be in radioresistant phases (S-phase, G1) at the time of administration of external-beam radiation (given in two-minutes every 24-hours).
  • [0276]
    Because of the great flexibility of the manufacturing process for production of multilayer radioactive microspheres of the present invention and the ability to produce multilayer radioactive microspheres containing over 220 different radionuclides, the half-life, energy, and activity of the multilayer radioactive microspheres can be precisely matched to the type and size of tumor being treated to deliver continuous low dose rate radiation at the proper rate to produce a sustained G-2 block.
  • [0277]
    Normally, the majority of cells in a tumor population are in radio resistant phases (quiescent somatic, resting phases) during the majority of the time, and only a small percentage of the population resides in radiosensitive phases. Thus, daily administration of fractionated external-beam radiation therapy results in irradiation of tumors composed mainly of cells that are radio resistant. The dose of conventional fractionated radiation required to control a radio resistant tumor cell population is relatively high (8,000 to 12,000 centi-Gray), and this dose is approximately 40 percent to 60 percent higher than what the surrounding normal tissues can tolerate.
  • [0278]
    For this reason, it is only possible to control approximately 30 percent of solid tumors (adenocarcinomas, squamous cell carcinomas, sarcomas, melanomas) treated by a conventional modern course of external-beam radiation therapy. This poor therapeutic ratio characteristic of conventional fractionated external-beam radiation therapy could be dramatically improved by modifying the radiosensitivity of the tumors under treatment. If tumors composed mainly of radiosensitive cells are irradiated in a conventional fashion, then the required tumor dose should be much lower. In fact, cell culture studies have indicated that cells blocked in G-2 phase can be killed by approximately half the dose of radiation normally required.
  • [0279]
    The amount of radiation that can be safely delivered by external means is limited by the surrounding normal tissues to a maximum of approximately 7,000 centi-Gray (cCy). This dose applied to a 5 centimeter diameter tumor composed largely of radio resistant cells results in approximately a 30 percent local control rate.
  • [0280]
    However, the same dose applied to a tumor composed largely of radiosensitive cells should result in a much higher local control rate. The tumor can be converted from one composed of radioresistant cells to one composed of radiosensitive cells by the permanent implantation of one or several multilayer radioactive microspheres which deliver continuous low dose rate irradiation at the proper rate to cause a sustained G-2 cell cycle block. Consequently, prior to administration of a conventional course of external-beam radiation therapy, implantation of one or several multilayer radioactive microspheres should dramatically increase the cure rate. This can be accomplished without an increased complication rate, because a relatively low total dose of radiation is delivered by the multilayer radioactive microspheres, and this dose is sharply localized due to the physical characteristics of the radionuclide.
  • [0281]
    If tumors treated by external-beam radiation therapy are first “radiosensitized” by implantation of one or several multilayer radioactive microspheres, then the seed implantation procedure may safely performed in a wide variety of human body sites without risk of complication caused by seed implantation. Because of the seed design, multilayer radioactive microspheres may be implanted into almost any body site using thin-caliber (21-gauge to 22-gauge) needles. Multilayer radioactive microspheres implantation performed using these thin gauge needles permits safe implantation without significant risk of bleeding or tissue trauma, and overlying loops of stomach or small intestine are usually not a contraindication.
  • [0282]
    In one system of therapy, a CT scanning system or other imaging system such as MRI (magnetic resonance imaging) is used to obtain images. A flat table is designed to attach over the standard curved CT scanner patient table. This table serves as a reference base for a stereotactic coordinate system. The table has built into the side rails X-ray markers that may be seen on the CT scout film, and allow determination of distance from a reference point on the Z-axis of the coordinate system.
  • [0283]
    The patient is immobilized on this table by means of straps or pins. A CT scan of the body is taken with images taken 0.20 to 2.0 centimeters apart. The area to be implanted with multilayer radioactive microspheres is determined by a physician, and a scan image (for example, image 5, Z=−90 millimeters) corresponding to the desired point of implantation is chosen. A semicircular arc composed of a material that is relatively transparent to X-ray images (titanium, or carbon filament) is then attached to the reference table at the level corresponding to the chosen scan image. A stereotactic instrument holder is attached to the arc or aiming bow.
  • [0284]
    The 21-gauge or 22-gauge implantation needle is inserted into the instrument holder. Stereotactic coordinates of the biopsy point are set on the aiming bow (arc) and instrument holder to direct the needle to the proper point, and adjustment are locked. A table slides the patient to the proper scan point, and using repeated CT scans through the chosen Z-coordinate slice, the needle is inserted into the target point within the patient under CT-guidance. The position of the needle tip is verified with a final CT scan when it is positioned in the center of the tumor to be implanted. The stylet is removed from the 21-G or22-G implantation needle, and the radioactive multilayer radioactive microspheres is placed into the hollow needle and implanted into the tissue by replacing the needle stylet.
  • [0285]
    In another such system, the flat table is designed to attach over the standard curved CT scanner patient table. This table serves as a reference base for the robotic coordinate system. The table has built into the side rails “Z-shaped” X-ray markers that may be seen on the CT scout film, and allow determination of distance from a reference point on the Z-axis of the coordinate system. A commercially-available robot arm containing six joints of rotation and a relative accuracy of 0.05 millimeters is attached to a gantry linked to the table base coordinate system. The robotic arm is modified in that the arm is constructed only of materials known not to interfere with CT scanning X-rays (titanium, carbon filaments).
  • [0286]
    The patient is immobilized on this table by means of straps or pins. A CT scan of the body is taken with images taken 0.20 to 2.0 centimeters apart. The area to be implanted with multilayer radioactive microspheres is determined by a physician, and a scan image (for example, image 5, Z=−90 millimeters) corresponding to the desired point of implantation is chosen. Spatial target coordinates are determined by selecting the target point on the chosen CT-slice, and these are translated into base-reference system coordinates and robotic arm coordinates. The robotic arm aims a spring-loaded needle injector (which is capable of instantaneously injecting a 21-gauge or 22-gauge thin-diameter needle through human tissues to any desired distance at 1 to 5 millimeters increments to a maximum depth of 40 centimeters) at the target point.
  • [0287]
    The base table slides patient to proper scan point, and the needle injector is fired, placing the needle tip instantaneously at the desired target point within the body. The correct position of the needle tip is verified with a final CT scan when it is positioned in the center of the tumor to be implanted. The stylet is removed from the 21-G or 22-G implantation needle, and the radioactive multilayer radioactive microspheres is mechanically injected into the hollow needle and implanted into the tissue by mechanically pushing the stylet through the needle behind the seed.
  • EXAMPLES
  • [0288]
    The following hypothetical nonlimited examples illustrate the invention:
  • Example 1
  • [0289]
    A patient has a malignant adenocarcinoma of the head of the pancreas which is inoperable because of its proximity to the celiac plexus and porta hepatis and measures 3.5 in length×2.0 centimeters in diameter. The patient receives external-beam radiation therapy, but the maximum deliverable dose is limited to 6,000 centi-Gray because of potential toxicity to the surrounding normal tissues. This dose of 60 Gray delivered over 6 weeks, 200 centi-Gray/fraction, 5 days/week is known to be inadequate to result in lasting local control of this radio resistant tumor. His chances for local tumor control are now less than 30 percent.
  • [0290]
    The tumor is needle biopsied, and cell culture of the tumor is accomplished, and the cells are exposed to various dose rates of continuous irradiation. It is determined using flow cytometry techniques that a sustained G-2 block occurs if the cells receive continuous irradiation at a rate of 25 to 50 centi-Gray per hour. Computerized radiation dosimetry indicates that two I-125 seeds containing 25 mCi each implanted 1.7 centimeters apart produce a dose of 35 centi-Gray/hour to a tumor target volume measuring 3.5 cm×2.0 cm.
  • [0291]
    Two spherical multilayer radioactive microspheres 0.30 millimeters in diameter and containing 25 mCi of radioactive I-125 as described above are obtained. The patient is taken to the CT scanner and placed on the special flat base table connected to the robot gantry. Scans are taken, the target points are chosen, and coordinates are calculated and translated into robot arm coordinates. The robot arm fires the spring loaded 21-G needle to the correct location within the pancreatic tumor, and the correct position is verified with CT scan. The first I-125 multilayer radioactive microspheres is injected and permanently implanted. Another 25 mCi multilayer radioactive microspheres is implanted 1.7 centimeters from the first using the same technique.
  • [0292]
    Repeat tumor biopsy is performed 5 days later, and using flow cytometry, it is found that more than 90 percent of the tumor cells are blocked at G-2. Now the radiation dose of 6,000 cGy will be twice as effective because the tumor is composed mainly of radiosensitive tumor cells blocked in G-2. The 6,000 centi-Gray will be biologically equivalent to a dose of 12,000 centi-Gray, and chances for tumor control are increased to over 90 percent. The radiation dose delivered by the I-125 seeds adds to the tumoricidal effect, in addition to producing a sustained G-2 block that results in radio sensitization to external-beam irradiation.
  • Example 2
  • [0293]
    A female patient with a malignant fibrous histiocytoma (MFH, soft tissue sarcoma) located in the presacral hollow and measuring 10 centimeters in diameter is determined to have an inoperable tumor due to bony invasion of the first sacral vertebral body. She is to receive a course of external-beam radiation therapy, but the maximum dose deliverable is limited to 7,000 centi-Gray in 7 weeks due to the poor tolerance of surrounding normal tissues including small bowel and colon. Her chances for local tumor control are less than 30 percent.
  • [0294]
    Cell culture of the tumor is successful, and cells are exposed to low dose rate irradiation. Flow cytometry studies indicate that radiation dose rates of 150 centi-Gray/hour are required to produce a sustained G-2 block, and thus render the sarcoma cells radiosensitive. Because of the high dose rates required to produce a G-2 block, the radioactive seed must have low energy to avoid irradiation adjacent structures.
  • [0295]
    Palladium-112 is chosen as the radionuclide with an energy of 18.5 KeV and half-life of 21.0 hours. Computerized radiation dosimetry indicates that ten seeds should optimally be implanted throughout the tumor volume. Ten spherical multilayer radioactive microspheres containing the required amount of Pd-112 and measuring less than 0.30 millimeters in diameter are manufactured according to the present disclosure.
  • [0296]
    The patient is taken to the CT scanner and the robotic arm is used to implant ten Pd-112 MRM's via a 21-G needle using CT guidance for verification. Repeat biopsy and cell culture with flow cytometry analysis indicates that more than 90 percent of cells are in G-2 block, and external-beam radiation therapy is initiated. The 7,000 cGy dose will be biologically equivalent to approximately 14,000 cGy due to radiosensitization and G-2 block produced by the multilayer radioactive microspheres. Tumor control probability is increased to over 90 percent. Because of the short half-life of the radionuclide, the robotic multilayer radioactive microspheres implantation procedure is repeated twice a week during the patient's external-beam radiation therapy (seven week course).
  • [0297]
    In FIG. 6, there is shown an intracavitary radiation-emitting capsule 30 having a plurality of radiation emitting microspheres 34A-34G, a stainless steel tube 36 and an end weld 38. The end weld 38 seals the tube 36 which contains the microspheres 34A-34G. The microspheres 34A-34G are of the type described in connection with FIGS. 1-5 and are selected for the therapeutic treatment desired. While only 7 are shown in FIG. 6, a larger number are normally used and there may be as many as 40 contained in a cylindrical tube that is 2.0 centimeters long and 1 millimeter in diameter.
  • [0298]
    While microspheres are shown in FIG. 6 as inserts to the intracavitary implant 30, other sizes and shapes may be used such as cylindrical bars or other geometric shaped radiating units. However, standard sizes manufactured by the electron bonding processes in quantities are desirable because of their economy and the ability to manufacture them with different radiation characteristics for flexibility of treatment. Moreover different shapes and sizes of containers may be used and the walls, instead of being of only one material, may include different materials or added materials to provide different amounts of shielding. For example a square tube may contain square radiating elements and include shielding and elements of different radiating intensities and characteristics.
  • [0299]
    A wide variety of radionuclides with energies varying from very low to very high can be incorporated into composite intracavitary sources by sealing multiple multilayer radioactive microspheres of one or several types into an appropriate container. Use of low energy intracavitary sources composed of low energy multilayer radioactive microspheres allows selective shielding of adjacent vital structures such as rectum and bladder using relatively thin high atomic weight foils placed over the intracavitary sources. Morever, a 1 millimeter diameter solid intracavitary source and a solid needle source can be manufactured by coating the rod or needle substrate with a radioactive coat, diffusion barrier coat and protective coat.
  • [0300]
    The intracavitary sources of the present invention eliminate the need for dilating openings because of their small size. For example: (1) the cervical canal or endocervical canal need not be dilated because the intracavitary multilayer radioactive microspheres or wires have an outside diameter not exceeding 1 millimeter and cervical applicator has an outside diameter of only 2 millimeters which can be easily inserted into the uterus without cervical dilation; (2) the diameter of the intracavitary multilayer radioactive microsphere applicator is less than that of a uterine sound; (3) an intraoperative brain tumor applicator has a diameter of only two millimeters; and (4) the 1 millimeter source can be placed in a balloon catheter and easily slipped through the urethra for intracavitary bladder tumor irradiation.
  • [0301]
    The intracavitary multilayer radioactive microspheres can be easily shielded, making possible effective in vivo shielding of critical normal tissues at risk for radiation toxicity such as the bladder and rectum adjacent to the cervix. Thus, a radiation dose distribution can be designed that suits the individual patient's anatomy. The intracavitary multilayer radioactive sources of the present invention are suitable for treatment of cervix and uterine cancer, bladder cancers, esophageal cancers, biliary duct cancers, brain tumors, and nasopharyngeal cancers.
  • [0302]
    In FIG. 7, there is shown another embodiment 42 of multilayer radiation emitting implant formed as a solid wire-like cylinder, without void spaces, and having a plurality of layers similar to the microspheres described in connection with FIGS. 1-5.
  • [0303]
    In the preferred embodiment, the radiation emitting implant 42 is substantially 10 to 20 centimeters long and has an outer diameter of approximately 0.15 to 0.40 millimeters in diameter. The intensity of its emission may vary along its length and may vary in intensity and half-life. Moreover, radioactive shielding may be coated on part of it. It has a sufficiently high yield point to permit bending to that it can be shaped in coordination with its radiation characteristics along its length to permit planned dosage in three dimensions through a tumor.
  • [0304]
    The wire-like implant 42 includes a central cylinder 44 and a plurality of tubular layers 45 concentric with the central cylinder 44 and bonded to each other. The central cylinder serves as a substrate upon which other layers, at least one of is a radiation emitter, are coated. The type of radiation emitting material is selected for appropriate intensity, to be beta particle or gamma ray emissive and for a predetermined half-life.
  • [0305]
    In the preferred embodiment, the central cylinder is 0.10 millimeter in diameter and made of tantalum and the layers are a holmium I-125 cylindrical tube 46, a hafnium nitride (HfN) cylindrical tube 48 and a titanium cylindrical tube 50, in the order named from the inside outwardly. The tube 46 is radiation emitting and may be applied at different thicknesses along the length of a wire-like implant by any of several methods to be described hereinunder. However, in the preferred embodiment, it is approximately 0.01 to 0.045 millimeters thick. The tube 48 is a diffusion barrier and substantially 0.005 to 0.05 millimeters in thickness and the tube 50 is a protective layer and is approximately 0.05 millimeter thick.
  • [0306]
    The multilayer radioactive wires of the present invention are used primarily for temporary removable implants. Instead of inserting bits of iridium wire into nylon tubing for afterloading (Rad/Irid Inc, Capitol Heights, Md.), a variety of different radionuclides incorporated into multilayered radioactive wires may be inserted into nylon or tissue compatible polyethylene tubing (American V. Mueller, American Hospital Supply Corporation) for temporary removable interstitial implants. These types of temporary removable implants are useful for implantation of tumors at accessible sites where the tubes penetrate the skin surface. Furthermore, a cut multilayer wire 1 millimeter in outer diameter may serve as an intracavitary source, or as a removable radioactive needle.
  • [0307]
    Temporary removable iridium-192 nylon ribbon implants have been used for treatment of head, neck, lung, vaginal, cervical, vulvar cancers, prostrate, breast, soft-tissue sarcomas and skin cancers. Radioactive wires placed in afterloading tubing may also be used for intracavitary treatment of esophageal cancer and biliary duct cancers (Klatskin's tumor) or bronchial lung cancers.
  • [0308]
    In FIGS. 8 and 9, there are shown a side sectional view and top sectional view of a ribbon-like radiation emissive implant 54 having a flexible ribbon-like connecting member 56 and a plurality of microsphere radiation emitters 58A-58C. The ribbon-like connecting member 56 acts as a rigid spacer between radiation emitters 58A-58C and allows multiple emitters to be implanted at once with a conventional thin gauge hollow needle by pushing the ribbon-like implant 54 out of the conventional tissue-embedded needle with a stylet while withdrawing the needle. The preferred rigid spacer material is metal with a diamond coat.
  • [0309]
    In the preferred embodiment, the ribbon and the ribbon-emitters 58A-58C may be implanted with a very thin 21 or 22-gauge needle. Although three radiation emitters are shown in FIG. 8, the ribbon-like implant 54 may be of any length and may contain any number of radiation emitters and any variety of different types of radiation emitters.
  • [0310]
    The ribbon-like implant 54 connects radioactive members internally by means of a thin metal ribbon or wire, rather than by an external suture, reducing the overall diameter. The ribbon-like connecting members are made rigid by locating lengths of tissue-compatible material over the connecting member between radiation emitters or by coating diamond-like carbon, or a low-atomic weight metal such as titanium or metal compound such as titanium nitride or zirconium carbide over the connecting member between emitters using sputtering or plasma deposition. This rigid structure may be pushed into tissues from the proximal rather than distal end while simultaneously withdrawing the interstitial needle or may be implanted rapidly using automatic implantation devices described hereinafter.
  • [0311]
    In the preferred embodiment, the connecting member 56 is a 0.01 millimeter ribbon, substantially square or a 0.01 millimeter wire made of tungsten and the microspherical emitters contain, as shown in connection with emitter 58B an inner sphere 60 welded to the connector 56.
  • [0312]
    In this embodiment, the central sphere is 0.10 millimeters in diameter and made of tantalum and the layers are a holmium I-125 sphere 62, a hafnium nitride sphere 64 and a titanium sphere 66, in the order named from the inside outwardly. The sphere 62 is radiation emitting and methods to be described herein under. In the preferred embodiment, it is approximately 0.01 to 0.045 millimeters thick. The sphere 64 is a diffusion barrier and substantially 0.005to 0.05 millimeters in a thickness and the sphere 66 is a protective layer and is approximately 0.05 millimeters thick.
  • [0313]
    The radiation emitters 58A-58C are optimized for individual tumor types so that permanent implants which deliver continuous low dose-rate irradiation over less than 130 days, may be used for slowly growing tumors such as prostate cancers, but because they may be less suitable for rapidly growing tumors such as glioblastomas, other shorter-lived emitters can be manufactured as needed by simply changing deposition parameters as discussed hereinafter. The ribbon-emitters are used mainly for permanent implants and the wire-emitters are used primarily for temporary-removable implants.
  • [0314]
    In FIGS. 10 and 11, there are shown a plan and a sectional view of a curved circular optical plaque 70 for applying radiation to the eye having a central radioactive layer 76, two outer steel or titanium supports 72A and 72B on either side of the radioactive layer 76, separated from the radioactive layer 76 by a corresponding two diffusion layers 78A and 78B. On the outside may be tissue compatible, anti-corrosive additional layers 80 and 82, if necessary. The layers form a section of a sphere with circumferentially spaced suture holes 74A-74H through it that provides a concave socket for applying a therapeutic dose of radiation inwardly to the eye.
  • [0315]
    To fit against the eye, the socket has a radius of curvature between 1.40 to 1.10 centimeters and the socket is formed in layers with no voids. The radioactive layer is low energy gamma emitter or beta emitter and may be a titanium-44 layer, an Sm-145, Sm-151, Tm-171 or I-125 layer having a thickness of about 0.01 to 0.045 millimeters. Titanium-44 provides 68-78 kiloelectron volts (KeV) of radiation a half life of 47 years. The cord length from edge to edge (diameter of plan view) is between 8 millimeters to 22 millimeters.
  • [0316]
    In FIG. 12, there is shown a plan view of another embodiment of optical plaque 70A similar in construction to the plaque of 70 except that one portion at 71 is cut away so as to fit close to the lens to avoid damage thereto. Generally, this type of optical plaque will have a cord diameter of between 20 to 22 millimeters. Similarly, FIG. 13 shows an embodiment having an arc shaped cut away compartment at 71A to provide space around the optic nerve so as to avoid damage thereto. This embodiment may range in size between 8 millimeters to 22 millimeters in cord size.
  • [0317]
    Similar sized plaques are shown in the embodiment 70C in FIG. 14 with a larger portion cut away for convenient fitting and three other embodiments 70D, 70E, and 70F are shown in FIGS. 15, 16 and 17 respectfully, all of which have multiple parts. The embodiment 70D of FIG. 15 is generally an 8 millimeter embodiment and is formed in two section divided along a hemispheric line whereas the embodiments 16 and 17 are formed in three sections having a central section and two end sections, with the embodiment 7F including an optic nerve cut away in one of the sections.
  • [0318]
    Other variations are possible and are designed to fit closely adjacent to the cancerous tissue with minimum overlapping that might unnecessarily irradiate healthy tissue. All of these embodiments are intended to provide a high radiation level such as 10,000 centi-Gray encompassing the cancerous tissue near the capular wall and retina with rapid attenuation so that a short distance out the energy level falls below 3,000 centi-Gray which is tolerable to the retina and optic nerve. Generally that drop occurs at a 30 percent isodose line.
  • [0319]
    In FIG. 18, there is shown a surgical radiation-emitting fabric 90 having a border strip 92 of X-ray opaque fiber, a fabric base 94 of cellulose fibers, and a plurality of radiation emitters 96 spaced throughout the fabric base 94. The radiation emitters 96 have basic structure of the microspheres of FIGS. 1-5 extending from it.
  • [0320]
    One embodiment of the fabric of this invention self-adheres to the tissues over which it is placed. The fabric may be either tissue-absorbable or non-tissue absorbable and may contain multiple multilayered radioactive microspheres. This construction allows rapid surgical implantation of multiple seeds without need of interstitial needles or a seed gun. The radiation emitters 96 may be spaced at 1.0 to 2.5 centimeter intervals embedded into a tissue compatible fabric. This fabric may be sewn intraoperatively into the tumor bed, or in the case of brain tumors, the fabric is simply laid over the area to be treated. It self-adheres to the tissues over which it is placed.
  • [0321]
    Two types of fabric multilayer radioactive microspheres are produced—tissue-absorbable fabric and non-tissue absorbable fabric. The tissue-absorbable fabric is also hemostatic and is suitable for intraoperative permanent implantation of the surgical bed in the chest, abdomen, extremity, or brain. Since the multilayer radioactive microsphere surgical fabric is hemostatic, it sticks to the tissues upon which is applied and need not be sutured.
  • [0322]
    However, it may be sutured in for additional immobilization if desired. The fabric eventually dissolves after several months, and tissue fibrosis caused by local seed irradiation holds the seeds in place. The tissue half-life of the fabric is made to match the radioactive half-life of the radioactive seeds. The non-tissue absorbable multilayer radioactive microsphere surgical fabric may be used in accessible body cavities.
  • [0323]
    To be clinically useful, the multilayered radioactive microspheres should contain a minimum of 0.50 millicuries (mCi) of radioactive material, and the multilayered radioactive wires or filaments should contain a minimum of 0.50 millicuries (mCi) of radioactive material per centimeter of length.
  • [0324]
    The basic structures described in connection with FIGS. 1-18 can be used in many different therapy modalities depending on the characteristics of the material in the implants. For example, a “mixed” gamma/electron seed or microfilament can be prepared to produce a combination of high dose beta irradiation of a grossly visible tumor mass coupled with a lower dose “regional” gamma irradiation that spares the surrounding normal tissues yet provides enough radiation dose to sterilize microscopic tumor extensions into the normal tissues.
  • [0325]
    Thus, the mixed beta/gamma seed or microfilament accomplishes two goals simultaneously—it safely delivers an extremely well-localized tumoricidal dose to the grossly visible tumor mass and delivers a lower radiation dose to the surrounding normal tissues that is sufficient to sterilize microscopic tumor emboli or infiltrations. A seed such as this effectively eliminates the need for external-beam irradiation of the surrounding normal tissues and greatly simplifies definitive cancer treatment. It also reduces treatment cost and patient inconvenience since a course of external irradiation normally takes five to eight weeks to complete.
  • [0326]
    The beta seed and beta microfilament allows the beta particles to escape into the patient's tumor tissues by employing a container that is essentially “transparent” to beta particles. If beta-radiation is the only desired seed emission, then in the beta-particle-producing seed design, a low-Z atomic center must be used to prevent the production of bremsstrahlung X-rays by interaction of the electrons with a high-Z material. If a combination of beta particles and X-rays is desired, then a high-Z material would be used for the seed substrate center.
  • [0327]
    Above dose rates of 150 cGy/hour, there is no sparing beyond that produced by conventional external beam irradiation. At dose rates of 5-20 cGy/hour, there is a marked sparing effect on normal tissues.
  • [0328]
    In clinical practice, permanently-implanted radioactive seeds with long half-lives have a biological advantage because they typically spare the adjacent normal tissue through a mechanism commonly known as “cellular repair of sublethal radiation damage” because they deliver cumulative radiation doses at very low dose rates over a long period of time. The disadvantage of radioactive seeds with long half-lives is that the cellular population of the tumor repopulates faster than cells are being killed by the low-dose-rate irradiation, resulting in clinical tumor recurrence and treatment failure.
  • [0329]
    On the other hand, seeds with short half-lives deliver their total radiation dose over a shorter period of time at much higher dose rates, resulting in somewhat less normal tissue sparing effect. They do produce a more rapid tumor cell killing effect, resulting in a more rapid clinical response.
  • [0330]
    These effects are combined into a single seed or radioactive microfilament design that contains radionuclides both with long and short half-lives. The short half-life component serves to get the tumor under control and reduce the tumor cell population without damaging the surrounding normal tissues. This radiation dose by itself does not result in permanent tumor cure but brings the tumor into remission. The second component of the seed is designed to deliver a large total radiation dose over an extended period of time without damaging the normal surrounding tissues, resulting in permanent tumor kill.
  • [0331]
    Multilayered radioactive implants that contain two or more different radionuclides with different half-lives, are produced by changing targets during the coating process. After one radionuclide or non-radioactive radionuclide precursor is coated, another can be coated over the first. The remainder of the seed or microfilament is manufactured as described above.
  • [0332]
    Neutron-producing microspheres and microfilaments consist of a substrate core that is coated by means of evaporation, sputtering, ion-beam sputtering, cathodic arc deposition, ion plating, or like means with either an alpha-particle-producing or gamma-producing material that is in turn coated with a light element target material that produces neutrons when irradiated by either high energy gamma rays or alpha particles produced by the inner coat. The energy produced by the alpha particle or gamma ray must be greater than the threshold energy of the target material used to produce the neutrons.
  • [0333]
    Since the alpha particles are very energetic, a wide variety of target elements may be used. With gamma-n sources, only two targets have a sufficiently low threshold energy to be useful—these are beryllium (1.67 MeV) and deuterium (2.23 MeV). The alpha-particle-producing or gamma-producing material can also be one that is initially non-radioactive but may be later activated by neutron activation in a neutron oven.
  • [0334]
    A microspherical substrate or microfilament is sputter-coated with an alpha-producing radioactive material from an alpha-producing radioactive sputter target. Alternatively, the coats may be produced by reactive coating from a radioactive alpha particle producing gas and a metal target. Examples of such materials would include radioactive americium-241 (t−1/2=458 years, alpha Energy (E)=5.5 MeVV, lead-210 (t−1/2=22 y, Alpha E=5.3 MeV), plutonium-238 (86 y, 5.5 MeV), actinium-225 (10.0 d, 5.7 MeV), actinium-227 (22 y, 4.94 MeV), americium-241 (458 y, 5.48 MeV), curium-242 (163 d, 6.1 MeV), curium-244 (18 y, 5.8 MeV), neptunium-237 (2 million y, 4.8 MeV), thorium-228 (1.9 y, 5.4 MeV), uranium-232 (74 y, 5.3 MeV), plutonium-239 (24,400 y, 5.1 MeV), polonium-210 (138 days,k 5.3 MeV), radium-226 (1620 years, 4.5-7.7 MeV), uranium-238 (4.2 MeV, 4.5×109 years).
  • [0335]
    Following sputter-deposition of a sufficient amount of this material onto the microspherical substrate (1-50 microns thick) then a sufficient amount of the target material (1-50 microns thick) is sputter-coated directly onto the radioactive alpha particle producing coat. Suitable target materials for this purpose includes aluminum, beryllium, boron, lithium, magnesium, and sodium. The preferred alpha-producing coating of the present invention is polonium-210, and the preferred target coatings are boron and beryllium. These targets produce neutrons with energies of 5.0 MeV and 10.8 MeV, respectively, following alpha particle bombardment by the polonium-210 coat.
  • [0336]
    In another design, the non radioactive elements may be sputter-coated, and the finished microspheres may be later activated in a neutron oven to produce the final alpha-n multilayered radioactive microspheres. For example, a batch of several thousand 400 micron titanium microspherical substrates are coated with 25 microns of bismuth. These are then coated with 25 microns of boron, followed by a 2 micron coat of chromium as a diffusion barrier and 50 microns of titanium as a protective coat.
  • [0337]
    The finished non radioactive microspheres are then placed into a neutron flux, and the bismuth is converted to polonium-210 (saturation 1500 microcuries/gm in a flux of 1012n/cm2/s). The polonium-210 then produces 5.3 MeV alpha particles that hit the adjacent boron target material, producing 5.0 MeV neutron irradiation over the lifetime of the polonium-210 (198 days). The neutrons produced in the boron coat exit through the titanium coat into the patient's tumor tissues.
  • [0338]
    In a similar fashion, several thousand 150 micron diameter microfilament substrates can be primed with 1 micron of chromium, then coated with 10 microns of bismuth, then coated with 10 microns of boron, 1 micron of chromium, and 30 microns of titanium to produce a neutron-emitting microfilament with an average lifetime of 198 days.
  • [0339]
    A microspherical substrate or microfilament is sputter-coated with a high-energy gamma-producing radioactive material from a gamma-producing radioactive sputter target. Alternatively, the coats may be produced by reactive coating from a radioactive high-energy gamma-producing gas and a metal target. Examples of such materials include radioactive antimony-124 (6% 2.09 MeV+98% 0.60 MeV, 60 d), radium-226+daughters, thorium-228+daughters, arsenic-76 (0.9% 2.08 MeV+44.6% 0.56 MeV, 26.5 hr), bismuth-207 (0.5% 2.47 MeV+98%0.56 MeV, 28 y), cobalt-56 (47% 2.5 MeV, 15% 3.25 MeV, 77 d), iodine-124 (2% 2.26 MeV, 51% 0.51 MeV, 4.0 d), lanthanum-140 (4% 2.54 MeV, 95% 1.60 MeV, 40.2 hr), rubidium-88 (2.5% 2.68 MeV, 23% 1.85 MeV), yttrium-88 (0.5% 2.76 MeV, 99.5% 1.84 MeV, 106 d).
  • [0340]
    Following sputter-deposition of a sufficient amount of this material onto the microspherical substrate (1 -50 microns thick) then a sufficient amount of the target material (1-50 microns thick) is sputter-coated directly onto the radioactive high-energy gamma producing coat. Suitable target materials for this purpose are beryllium and deuterium. The preferred high-energy gamma producing coatings of the present invention include antimony-124 and arsenic-76. The preferred target coating is beryllium. This target produces neutrons with relatively low energies of 0.248 MeV.
  • [0341]
    In another design, the non radioactive elements may be sputter-coated, and the finished microspheres may be later activated in a neutron oven to produce the final gamma-n multilayered radioactive microspheres. For example, a batch of several thousand 400 micron titanium microspherical substrates could be coated with 25 microns of antimony or arsenic. These are then coated with 25 microns of beryllium, followed by a 2 micron coat of chromium as a diffusion barrier and 50 microns of titanium as a protective coat. The finished non radioactive microspheres are then placed into a neutron flux, and the antimony is converted to antimony-124 (Sb-124, saturation 140 mCi/gm in a flux of 1012n/cm2/s) and arsenic is converted to As-76 (saturation 920 mCi/gm in neutron flux). The Sb-124 or As-76 then produces 2.1 MeV gamma rays that hit the adjacent beryllium target material, producing 0.248 MeV neutron irradiation over the lifetime of the Sb-124(86 days) or As-76 (38 hrs). The neutrons produced in the boron coat exit through the titanium coat into the patient's tumor tissues.
  • [0342]
    In a similar fashion, several thousand 150 micron diameter microfilament substrates could be primed with 1 micron of chromium, then coated with 10 microns of antimony or arsenic, then coated with 10 microns of beryllium, 1 micron of chromium, and 30 microns of titanium to produce a neutron-emitting microfilament with an average lifetime of 86 days.
  • [0343]
    To control the energy level of X-rays produced by an implant, beta particle energy is modulated prior to the collision of the beta particle with a bremsstrahlung coat.
  • [0344]
    The beta particle energies are modulated by applying a low atomic weight coat (Z<40) over a beta particle producing coat. The thicker the coat, the lower the beta particle energy. Also, the energy degradation of the beta particle is controlled by the coat thickness and by the Z or E of the modulation material as well as the modulation material density. The starting energy of the beta particle should be less than 500 KeV to degrade the value using maximum modulating coats up to 100 microns thick.
  • [0345]
    To tailor low X-ray energies emitted from multilayered radioactive microspheres or microfilaments, a radioactive seed is prepared that consists of microspherical or microfilament substrate uniformly coated by an electron-producing (beta particle) radioactive coat with a kinetic energy modulation layer, that is in turn coated by a bremsstrahlung X-ray producing coat, that is in turn coated by a K-fluorescent or L-fluorescent low energy X-ray producing coat. The seed is finished with a protective tissue-compatible coat.
  • [0346]
    In another design, a radioactive microsphere or microfilament consists of a substrate uniformly coated by an electron-producing (beta particle) radioactive coat with a kinetic energy modulation layer, that is in turn coated by a bremsstrahlung X-ray producing coat, that is in turn coated by an Auger low energy electron producing coat, that is in turn coated by another bremsstrahlung X-ray producing coat. The seed is finished with a protective tissue-compatible coat.
  • [0347]
    In another design, a radioactive microsphere or microfilament consists of a substrate that is uniformly coated by an electron-producing (beta particle) radioactive coat with a kinetic energy modulation layer, that is in turn coated by a bremsstrahlung X-ray producing coat, that is in turn coated by an element that produces a mixture of Auger electrons and low energy K-fluorescence or L-fluorescence X-rays, that is in turn coated by another bremsstrahlung X-ray producing coat to produce additional low energy X-rays from the Auger electrons. The seed is finished with a protective tissue-compatible coat.
  • [0348]
    In another design, the microsphere or microfilament substrate itself serves as the target source of bremsstrahlung radiation after bombardment by a radioactive beta-producing coat. The beta particle kinetic energy modulation coat is therefore placed between the beta-particle coat and the non-radioactive central substrate material. After beta-particle bombardment, the central core emits bremsstrahlung X-rays that travel back through the modulation and beta radioactive coats into the K-fluorescent/L-fluorescent coat and Auger target coats. The K-fluorescent coat is stimulated by the bremsstrahlung radiation to emit additional lower energy X-rays. Likewise, the Auger target coat is stimulated by the bremsstrahlung radiation to emit lower energy beta particles. Thus, the Auger coat needs to be flanked on the inside and outside by two additional bremsstrahlung target coats. Finally, a tissue-compatible protective coat such as titanium and an optional finishing coat such as diamond-like carbon is applied to finish the manufacture of the radioactive fluorescent microspheres or microfilaments.
  • [0349]
    More specifically, this implant includes nine coats. The first coat is a central microspherical or microfilament core that is composed of an efficient bremsstrahlung-producing high-Z material such as hafnium, tantalum, tungsten, rhenium, osmium, or uranium. This high-Z core also serves as an X-ray marker that permits visualization of the seed implanted into human tissues. Bremsstrahlung X-ray production is proportional to Z2. The average energy of the photons produced will be about ⅓ of the modulated beta energy.
  • [0350]
    The second coat is a beta-particle kinetic energy (KE) modulation coat that serves to slow the beta particles before they collide with the bremsstrahlung target material in the central core. The preferred kinetic energy modulation coats are low-Z materials including carbon graphite, diamond-like carbon, diamond, aluminum, titanium, vanadium, and chromium.
  • [0351]
    The third coat is the radioactive beta-particle producing coat. This produces beta particles that have kinetic energies of between 5 KeV and 500 KeV. It is desirable to have a radioactive coat that produces only beta particles without significant gamma-ray production. In this manner, an excess amount of beta-producing radioactive material can be placed in the coat to overcome the inherent inefficiency of the bremsstrahlung X-ray production process. The preferred radioactive beta-particle-producing radionuclides for this coat include Pd-112, Tm-165, Ni-66, U-237, Er-169, P-33, W-185, S-35, Os-194, H-3 (tritium), Ru-106, Pb-210, and Sr-90. The fourth coat is a diffusion barrier such as chromium nitride or titanium nitride is coated over the radioactive coat to prevent atomic leakage into the outer seed coats.
  • [0352]
    The fifth coat is a K-fluorescent or L-fluorescent target material coated over the diffusion barrier coat. This coat would produce characteristic low energy X-rays (5-60 KeV) when bombarded by white bremsstrahlung X-rays produced by the stimulated central core high-Z material. Preferred materials for this fluorescent X-ray coat consist of zirconium, molybdenum, palladium, silver, cadmium, indium, tin, antimony, and tellurium.
  • [0353]
    The sixth coat is a secondary bremsstrahlung coat. This coat is again composed of a thin layer of a high-Z material such as tungsten. It is placed adjacent to the seventh coat which is the Auger electron producing coat. Lower energy X-rays are produced by bremsstrahlung from the low energy Auger electrons stimulated by the bremsstrahlung radiation originating from the central core material.
  • [0354]
    The seventh coat is the Auger electron target coat. This coat serves to produce Auger electrons due to stimulation from bremsstrahlung X-rays produced in the central core material. The low energy Auger electrons are utilized to produce even lower bremsstrahlung X-rays as they strike the adjacent high-Z target materials. Preferred Auger electron-producing materials would have Z-values below 30. Preferred target materials for this purpose include titanium, vanadium, chromium, nickel, copper, zinc, and aluminum.
  • [0355]
    The eighth coat is a secondary bremsstrahlung coat. This coat is composed of a thin layer of a high-Z material such as tungsten. It is also placed adjacent to the seventh coat, the Auger electron producing coat.
  • [0356]
    The ninth coat is an optional marker coat. This thin coat is composed of a paramagnetic material such as samarium that is easily visualized on conventional magnetic resonance imaging scanners.
  • [0357]
    The tenth coat is a protective coat. This -is a relatively thick coat designed to mechanically protect the inner coats. Preferred materials for this coat include relatively low-Z materials that have a high corrosion-resistance and good human tissue compatibility such as titanium, vanadium, and chromium.
  • [0358]
    The eleventh coat is an optional outer coat. This coat is designed to impart additional corrosion resistance, improve friction reduction, impart additional hardness and smoothness, and or to add colors. Preferred materials include diamond-like carbon or diamond coats, titanium nitride, hafnium nitride, tungsten nitride, or tantalum nitride.
  • [0359]
    The preferred radioactive coats used in the production of fluorescent X-ray producing radioactive seeds and wires of the present invention are shown in tables 123 and 124.
  • [0360]
    Since a relatively high level of radioactivity may be needed in the beta-particle coat to produce sufficient bremsstrahlung radiation, beta-producing radionuclides are preferred that do not also produce gamma rays. Therefore, the preferred radionuclides produce beta particles with essentially no gamma component. Additionally, the electron energy must be below approximately 500 KeV. These energies may be modulated downward using a low-Z coating.
  • [0361]
    The preferred beta particle energy modulation coatings consist of materials that will slow but not shield the beta particles. These are listed in table 125. The R (in microns) or average distance that the beta particles travel multiplied by 25% and 50% corresponds roughly to the coating thickness (in microns) of listed material required to reduce the KE of the beta particles by 25% and 50%, respectively.
  • [0362]
    The preferred target materials used to produce bremsstrahlung X-rays from the beta particle collisions are listed in table 126. The bremsstrahlung material is a coating applied over the beta-KE modulation coat that is in turn placed over the radioactive beta-particle-producing coat. To obtain the most efficient conversion of beta particle KE to bremsstrahlung radiation, higher Z target materials are preferred since the energy radiated is approximately proportional to E×Z.
    TABLE 62
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Sb-119 36.1 hrs 23.9 KeV Sb-119H3
    Sb-119Cl5
    Sb-125 2.8 yrs 427-636 KeV Sb-125H3
    Sb-125Cl5
  • [0363]
    [0363]
    TABLE 63
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    As-73 80.3 days 53.4 KeV As-73CL3
    As-73F5
    As-73H3
    As-74 17.8 days 595 KeV As-74Cl3
    As-74F5
    As-73H3
    As-77 38.8 hours 239 KeV As-77Cl3
    As-77F5
    As-77H3
  • [0364]
    [0364]
    TABLE 64
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Bi-210 5.0 days 1.16 MeV Bi-210H3
    Beta
  • [0365]
    [0365]
    TABLE 65
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Br-77 57.0 hours 87.0-818 KeV (Br-77)2
    Br-77F1′5
  • [0366]
    [0366]
    TABLE 66
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ca-45 163.8 days 257 KeV Ca-45S
    Beta Particle Ca-45F
  • [0367]
    [0367]
    TABLE 67
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Cd-109 450 days 88 KeV Cd-1090
    Cd-113m 13.7 years 590 KeV Cd-113mO
    Beta Particle
    Cd-115m 43 days 935 KeV Cd-115mO
    (0.9%)
    1.62 MeV
    Beta Particle
  • [0368]
    [0368]
    TABLE 68
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ce-141 33 days 145 KeV Ce-141F3
    Ce-141Te
  • [0369]
    [0369]
    TABLE 69
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Cs-129 32.3 hours 371-412 KeV Cs-129Br2Cl
    Cs-131 9.7 days 4.0-30.0 KeV Cs-131Br2Cl
    Cs-135 1000 years 210 KeV Cs-135Br2
    Beta Particle
    Cs-137 30.2 years 662 KeV Cs-137Br2Cl
  • [0370]
    [0370]
    TABLE 70
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Cr-48 21.6 hours 116-305 KeV Cr-4802Cl2
    Cr-51 27.0 days 320 KeV Cr-5102Cl2
  • [0371]
    [0371]
    TABLE 71
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Dy-166 81.6 hours 82.5 KeV Dy-166F3
    (400 KeV Beta) Dy-166Cl3
    Dy-159 144 days 326 KeV Dy-159F3
    Dy-159Cl3
  • [0372]
    [0372]
    TABLE 72
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Er-169 9.4 days 8.42 KeV Er-169F3
    340 KeV Beta Er-169Cl3
    Er-169Br3
  • [0373]
    [0373]
    TABLE 73
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Eu-155 4.7 years 105 KeV Eu-155Cl3
    Eu-155F3
    Eu-155S
  • [0374]
    [0374]
    TABLE 74
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ga-67 78.3 hours 93-394 KeV (Ga-67)2H6
    Ga-67Cl3
  • [0375]
    [0375]
    TABLE 75
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Gs-159 18.6 hours 364 KeV Gd-159Cl3
    Gd-159F3
  • [0376]
    [0376]
    TABLE 76
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ge-68 280 days 92 KeV Ge-68F3Cl
    Ge-68Cl2F2
    Ge-68H4
    Ge-71  11 days 92 KeV Ge-71F3Cl
    Ge-71Cl2F2
    Ge-71H4
  • [0377]
    [0377]
    TABLE 77
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Au-193 17.6 hours 112-439 KeV Au-193S
    Au-198  2.7 days   412 KeV Au-198S
    Au-199  3.1 days 158-208 KeV Au-199S
  • [0378]
    [0378]
    TABLE 78
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Hf-181 42 days 133-482 KeV Hf-181Cl2
    Hf-181F4
  • [0379]
    [0379]
    TABLE 79
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ho-166 1.1 days 80.5 KeV Ho-166Cl3
    1.8 MeV Ho-166F3
     Beta Part.  
  • [0380]
    [0380]
    TABLE 80
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    In-111 2.8 days 170-245 KeV In-111F3
    In-114m  50 days 191-724 KeV In-114mF3
  • [0381]
    [0381]
    TABLE 81
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    I-125 59.9 days 35.5 KeV  (I-125)2
    I-125F5
    HI-125
    AgI-125
    Al(I-125)3
    I-129   1000 years  189 KeV (I-129)2
    Beta Part.   I-129F5
    (39.6 KeV    I-129
    gamma)
    AgI-129
    Al(I-129)3
    I-131  8.0 days 364 KeV (I-131)2
    I-131F5
    I-131
    AgI-131
    Al(I-125)3
  • [0382]
    [0382]
    TABLE 82
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ir-189 13.2 days 245 KeV Ir-189F6
    Ir-18903
    Ir-192 73.8 days 205-604 KeV   Ir-192F6
    Ir-19203
  • [0383]
    [0383]
    TABLE 83
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Fe-52 8.2 hours 168-377 KeV Fe-52 (CO)5
    Fe-52F3
  • [0384]
    [0384]
    TABLE 84
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    La-140 40 hours 408-815 KeV La-140Cl3
  • [0385]
    [0385]
    TABLE 85
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    PB-210 21 years 46.5 KeV gamma Pb-210F4
    15-61 KeV Pb-210Te
    Beta Particle
  • [0386]
    [0386]
    TABLE 86
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Lu-173 1.4 years 78-271 KeV Lu-173F3
    Lu-174 3.3 years 76.6 KeV Lu-174F3
    Lu-176m 3.6 hours 88.3 KeV Lu-176mF3
    Lu-177 6.7 days 113-332 KeV Lu-177F3
  • [0387]
    [0387]
    TABLE 87
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Hg-197 65 hours 69-77 KeV Hg-197
    Hg-197Br2
    Hg-197F
    Hg-195m 40.0 hours 262 KeV Hg-195m
    Hg-195mBr2
    Hg-195F
    Hg-197m 23.8 hours 134 KeV Hg-197m
    Hg-197mBr2
    Hg-197F
  • [0388]
    [0388]
    TABLE 88
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Mo-99 65.9 hours 144-739 KeV Mo-99F6
    Mo-99OF4
    Mo-99Cl5
    Mo-93 3500 years   30.4 KeV Mo-93F6
    Mo-93OF4
  • [0389]
    [0389]
    TABLE 89
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Nd-147 10.9 days 91-531 KeV Nd-147I3
  • [0390]
    [0390]
    TABLE 90
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Nb-92M 10.1 days 934 KeV Nb-92Mf5
    Nb-92mCl5
    Nb-93m 13.6 years 30.4 KeV  Nb-93mF5
    Nb-93mCl5
  • [0391]
    [0391]
    TABLE 91
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Nd-147 11 days 91 KeV Nd-147F3
    Nd-147Cl3
  • [0392]
    [0392]
    TABLE 92
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ni-63 92.0 years  67 KeV Ni-63(CO)4
    Beta Particle
    Ni-66 54.6 hours 200 KeV Ni-66(CO)4
    Beta Particle
  • [0393]
    [0393]
    TABLE 93
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Os-182 21.5 hours 131-510 KeV Os-182F6
    Os-182O4
    Os-191 15.4 days 129.4 KeV Os-191F6
    Os-191O4
    Os-194  6.0 years 42.9 KeV Os-194F6
    (10% gamma)
    54.0 KeV Os-194O4
    Beta Particle
  • [0394]
    [0394]
    TABLE 94
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    P-32 14.3 days 1.71 MeV P-32H3
    Beta Particle P-32F5
    P-32Cl2F3
    P-33 25.3 days 249 KeV P-33H3
    P-33F5
    P-33Cl2F3
  • [0395]
    [0395]
    TABLE 95
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Pr-143 13.6 days 935 KeV Pr-143Cl3
    Beta Particle Pr-143F3
  • [0396]
    [0396]
    TABLE 96
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Pu-237 45.1 days 59.5 KeV Pu-237F6
    gamma
    Pu-246- 10.9 days 44-224 KeV Pu-246F6
    gamma
    150-330 KeV
    Beta Particle
  • [0397]
    [0397]
    TABLE 97
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    K-42 12.4 hours 3.52 MeV K-42H
    Beta Particle
  • [0398]
    [0398]
    TABLE 98
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Re-181 20.0 hours 177-365 KeV Re-181F6
    Re-1810F4
    Re-18103Br
    Re-183 70.0 days 163 KeV Re-183F6
    Re-183OF4
    Re-18303Br
    Re-186 3.7 days 1.07 MeV Re-186F6
    Beta Particle Re-1860F4
    Re-18603Br
    Re-187 1000 years 8 KeV Re-187F6
    Beta Particle Re-1870F4
    Re-18703Br
  • [0399]
    [0399]
    TABLE 99
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Rh-105 35.4 hours 306-319 KeV Rh-105Cl3
    Rh-10502
  • [0400]
    [0400]
    TABLE 100
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Rb-87 1000 years 274 KeV Rb-187Cl
    Beta Particle Rb-187F2
  • [0401]
    [0401]
    TABLE 101
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ru-97 2.9 days 216-461 KeV Ru-97F5
    Ru-97Cl3
    Ru-106 367 days 39.2 KeV Ru-1065
    Beta Particle Ru-10603
  • [0402]
    [0402]
    TABLE 102
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Sm-151 93 years 55-76 KeV Sm-151
    Beta Particle
    Sm-153 46.7 hours 103 KeV Sm-153
    Sm-145 340 days 61.3 KeV Sm-145
  • [0403]
    [0403]
    TABLE 103
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Sc-47 3.4 days 159 KeV Sc-47F3
  • [0404]
    [0404]
    TABLE 104
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Se-72 8.4 days 46.0 KeV Se-72H2
    Se-72F6
    Se-7203
    Se-79 1000 years 154 KeV Se-73H2
    Beta Particle Se-73F6
    Se-7303
  • [0405]
    [0405]
    TABLE 105
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ag-111 7.5 days 250-340 KeV Ag-111N3
    1.0 MeV
    Beta Particle
  • [0406]
    [0406]
    TABLE 106
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Si-32 650 years 210 KeV Si-32H4
    Beta Particle Si-32H
    Si-32F4
    Si-320
  • [0407]
    [0407]
    TABLE 107
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Sr-83 32.4 hours 763 KeV Sr-8302
    Sr-83s
    Sr-85 64.8 days 514 KeV Sr-8502
    Sr-85s
    Sr-89 50.5 days 1.49 MeV Sr-8902
    Beta
    Sr-89s
    Sr-90 29.0 years 546 KeV Sr-9002
    Beta
    Sr-90s
  • [0408]
    [0408]
    TABLE 108
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    S-35 87.2 days 167 KeV S-32Cl4
    Beta Particle S35F6
    S-3502
    H2S-35
  • [0409]
    [0409]
    TABLE 109
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ta-177 2.4 days 113 KeV Ta-177F8
    Ta-177I5
    Ta-177S
    Ta-180m 8.2 hours 93.3-103 KeV Ta-180mF8
    Ta-180mI5
    Ta-180S
    Ta-182 115 days 100-1221 KeV Ta-182F8
    Ta-182I5
    Ta-182S
  • [0410]
    [0410]
    TABLE 110
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Tc-99m 6 hours 140 KeV Tc-99m
    (Tc-99m)207
    Tc-99 1000 years 292 KeV Tc-99
    Beta Particle (Tc-99)207
  • [0411]
    [0411]
    TABLE 111
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Te-123m 117 days 88-159 KeV Te-123mH2
    Te-123mF6
    Te-123mF4
    Te-125m 58.0 days 35.5 KeV Te-125mH2
    Te-125mF6
    Te-125mF4
    Te-127m 109 days 88.3 KeV Te-127mH2
    Te-127mF6
    Te-127mF4
    Te-132 78.2 hours 49.7-228 KeV Te-132H2
    Te-132F6
    Te-132F4
  • [0412]
    [0412]
    TABLE 112
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Tb-151 17.6 hours 108-731 KeV Tb-151Se
    Tb-151Te
    Tb-151Cl3
    Tb-155 5.3 days 86.5-105.3 KeV Tb-155Se
    Tb-155Te
    Tb-155Cl3
    Tb-160 73 days 298 KeV Tb-160Se
    Tb-160Te
    Tb-160Cl3
    Tb-161 6.9 days 25.6-74.6 KeV Tb-161Se
    Tb-161Te
    Tb-161Cl3
  • [0413]
    [0413]
    TABLE 113
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Th-231 25.5 84.2 KeV gamma Th-231
    299 KeV Th-231F4
    Beta Particle Th-231I4
    Th-23102
    Th-234 24.1 days 63.3-92.7 KeV Th-234
    (C5H702)4
    Th-234F4
    Th-234I4
    Th-23402
  • [0414]
    [0414]
    TABLE 114
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Sn-117 14 days 159 KeV Sn-117H4
    Sn-117BrCl3
    Sn-117Cl4
    Sn-117CLBr3
    Sn-117Te
    Sn-119m 245 days 24.0-65.0 KeV Sn-119mH4
    Sn-119mBrCl3
    Sn-119mCl4
    Sn-119mClBr3
    Sn-119mTe
    Sn-121 76 years 37 KeV Sn-121H4
    Sn-121BrCl3
    Sn-121Cl4
    Sn-121ClBr3
    Sn-121Te
    Sn-123 129.2 days 1.43 MeV Sn-123H4
    Beta Particle Sn-123BrCl3
    Sn-123Cl4
    Sn-123ClBr3
    Sn-123Te
  • [0415]
    [0415]
    TABLE 115
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Ti-44 48 years 68-78 KeV Ti-44Cl4
    Ti-44Br4
    Ti-44F4
    Ti-45 3.1 hours 1.04 MeV Ti-45Cl4
    Beta Particle Ti-45Br4
    Ti-45F4
  • [0416]
    [0416]
    TABLE 116
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Tl-201 3.05 days Hg K-X-ray Tl-201CL
    136-167 KeV Tl-201Cl2
    Tl-201F2
    (Tl-201)20
    Tl-201I
    Tl-202 12.2 days 439 KeV Tl-202Cl
    Tl-202Cl2
    Tl-202F2
    (Tl-202)20
    Tl-202I
    Tl-204 3.8 years 763 KeV Tl-204Cl
    Beta Particle Tl-204Cl2
    Tl-204F2
    (Tl-204)20
    Tl-204I
  • [0417]
    [0417]
    TABLE 117
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Tm-165 30.1 hours 84.2 KeV Tm-165Br3
    100 KeV Tm-165Cl3
    Beta Part. Tm-165F3
    Tm-165I32
    Tm-167 9.4 days 208 KeV Tm-167Br3
    Tm-167Cl3
    Tm-167F3
    Tm-167I32
    Tm-170 128.6 days 883 KeV Tm-170Br3
    Beta Part. Tm-170Cl3
    Tm-170F3
    Tm-170I32
  • [0418]
    [0418]
    TABLE 118
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    H-3 12.26 years 18.6 KeV H-32
    Beta Particle
  • [0419]
    [0419]
    TABLE 119
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    W-185 76 days 432 KeV W-185F6
    Beta Part. W-185 (CO)6
    (0.019% 125 gamma)
    W-187 1 day 479-685 KeV W-187F6
    W-187 (CO)6
  • [0420]
    [0420]
    TABLE 120
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    U-231 4.2 days 25.6-84.2 KeV U-231F6
    U-231F5
    U-231F4
    U-231Cl5
    U-231I4
    U-237 6.75 days 59-208 KeV U-237F6
    248 KeV U-237F5
    Beta Part. U-237F4
    U-237Cl5
    U-237I4
  • [0421]
    [0421]
    TABLE 121
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    V-48 15.9 days 984 KeV V-48F5
    V-48Cl4
    V-480Cl3
  • [0422]
    [0422]
    TABLE 122
    RADIOACTIVE
    REACTIVE
    ISOTOPE HALF-LIFE ENERGY SPUTTER-GAS
    Zr086 16.5 hours 243 KeV Zr-86Cl4
    Zr-86F4
    Zr-860
    Zr-88 83.4 days 393 KeV Zr-88Cl4
    Zr-88F4
    Zr-880
    Zr-93 1000 years 30.4 KeV Zr-93Cl4
    (gamma)
    60 KeV Zr-88F4
    Beta Part. Zr-880
  • [0423]
    [0423]
    TABLE 123
    Radio- Beta Particle
    nuclide T-½ Energy Gamma Compn.
    Pd-112 21.0 hours 300 KeV 20% 18.5 KeV
    Th-231 25.5 hours 299 KeV 100% 84.2 KeV
    Tm-165 30.1 hours 100 KeV 0.004% 15-60.4 KeV
    Ni-66 54.6 hours 200 KeV
    Dy-166 81.5 hours 400 KeV 100% 82.4 KeV
    U-237 6.75 days 248 KeV 59-208 KeV
    Er-169 9.6 days 340 KeV 0.1% 8 KeV
    Pu-246 10.9 days 150-350 KeV 44-224 KeV
    P-33 25.3 days 249 KeV
    W-185 74.8 days 433 KeV 0.01% 125 KeV
    S-35 87.2 days 167 KeV
    Os-194 6.0 years 54 KeV 10% 43.0 KeV
    H-3 12.26 years 18.6 KeV
    Ca-45 163.8 days 257 KeV
  • [0424]
    [0424]
    TABLE 124
    Radio- Beta Particle
    nuclide T-½ Energy Gamma Compn.
    Ru-106 367 days 39.2 KeV
    Pb-210 21 years 15-61 KeV 4.1% 46.5 KeV
    Sr-90 29.0 years 546 KeV
    Ni-63 92.0 years 67 KeV
    Sm-151 93 years 55-76 KeV 21.6 KeV
    Si-32 650 years 210 KeV
    Se-79 1000 years 154 KeV
    Rb-87 1000 years 274 KeV
    Zr-93 1000 years 60 KeV
    Tc-99 1000 years 292 KeV
    Pd-107 1000 years 35 KeV
    I-129 1000 years 189 KeV 39.6 KeV
    Cs-135 1000 years 210 KeV
    Re-187 1000 years 8 KeV
    Ra-228 1000 years 24-48 KeV 10-26 KeV
  • [0425]
    [0425]
    TABLE 125
    100 KeV
    Z R (micron)
    Atomic Density Distance
    Coating Number gm/cm x25%/x50%
    Carbon 6 3.51 36/72
    Auminum 13 2.7 46/—
    Titanium 22 4.5 28/56
    Vanadium 23 5.96 21/42
    Chromium 24 7.20 17/35
  • [0426]
    [0426]
    TABLE 126
    Z M
    Atomic Atomic
    Coating Symbol Number Weight
    Hafnium Hf 72 178.5
    Tantalum Ta 73 180.9
    Tungsten W 74 183.8
    Rhenium Re 75 186.2
    Osmium Os 76 190.2
    Uranium U 92 238.0
  • [0427]
    [0427]
    TABLE 127
    Z
    Atomic
    Coating Symbol Number
    Zirconium Zr 40
    Molybdenum Mo 42
    Palladium Pd 46
    Silver Ag 47
    Cadmium Cd 48
    Indium In 49
    Tin Sn 50
    Antimony Sb 51
    Tellurium Te 52
  • [0428]
    [0428]
    TABLE 128
    Z
    Atomic
    Coating Symbol Number
    Magnesium Mg 12
    Aluminum Al 13
    Silicon Si 14
    Phosphorous P 15
    Titanium Ti 22
    Vanadium V 23
    Chromium Cr 24
    Nickel Ni 28
    Copper Cu 29
  • [0429]
    [0429]
    TABLE 129
    Sphere, 200 micron substrate
    25 micron coat: 12.5 Ci/gram
    Sphere, 300 micron substrate
    25 micron coat: 6.0 Ci/gram
    Sphere, 400 micron substrate
    25 micron coat: 3.52 Ci/gram
    Sphere, 600 micron substrate
    25 micron coat: 1.63 Ci/gram
    Sphere, 600 micron substrate
    50 micron coat: 750 mCi/gram
    Microfilament 400 micron substrate (8-0 suture)
    10 micron coat: 388 mCi/gram
    Microfilament 300 micron substrate (9-0 suture)
    25 micron coat: 196 mCi/gram
    Microfilament 300 micron substrate (9-0 suture)
    30 micron coat: 161 mCi/gram
    Microfilament 150 micron substrate
    10 micron coat: 1.00 Ci/gram
    Microfilament 150 micron substrate
    25 micron coat: 360 mCi/gram
    Microfilament 150 micron substrate
    50 micron coat: 159 mCi/gram
    Microfilament 15 micron substrate
    10 micron coat: 3.9 Ci/gram
    Microfilament 15 micron substrate
    20 micron coat: 1.59 Ci/gram
  • [0430]
    [0430]
    TABLE 130
    RADIOACTIVE MICROSPHERES, 200 MICRON SUBSTRATE FOR
    PERMANENT IMPLANTATION INTO TISSUE 25 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Dysprosium
    Dy 790 Barns 57 Ci/g/4 h Dy-165 2.35 hrs 95-630 KV Dy-159
    Dy-166
  • [0431]
    [0431]
    TABLE 131
    RADIOACTIVE MICROSPHERES, 300 MICRON SUBSTRATE
    FOR PERMANENT IMPLANTATION INTO TISSUE
    25 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Gold
    Au  98 Barns 6.2 Ci/g/wk Au-198 2.7 d 412 KeV Au-199
    8.0 Ci/g/wk
    Holmium
    Ho  60 Barns 2.7 Ci/g/wk Ho-166 27 hrs  80 KeV
    5.9 Ci/g/satn.
    Lutecium
    Lu 100 Barns 4.3 Ci/g/wk Lu-177 6.7 d 210 KeV Lu-176m
    8.5 Ci/g/wk Yb-169
    8.3 Ci/g/sat. Yb-175
  • [0432]
    [0432]
    TABLE 132
    RADIOACTIVE MICROSPHERES, 600 MICRON SUBSTRATE
    FOR PERMANENT IMPLANTATION INTO TISSUE
    25 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Rhenium
    Re 44 Barns 2.5 Ci/g/wk Re-186 90 hr 137 KeV + Re-188
    3.8 Ci/g/satn. 1.07 MeV Beta
    Re 43 Barns 2.4 Ci/g/24 h Re-188 17 hr 155 KeV + Re-186
    3.8 Ci/g/wk 2.12 MeV Beta
    Samarium
    Sm 37 Barns 1.2 Ci/g/24 hr Sm-153 47 hr 100 KeV Sm-155
    3.5 Ci/g/wk Eu-155
    4.0 Ci/g/satn. Eu-156
    Enriched Calcium-46
    Ca-46 Depends on Sc-47 3.4 d 160 KeV Ca-45
    Enrichment Ca-47
    Ca-49
    Sc-49
    Praseodymium
    Pr 11.0 Barns 0.75 Ci/g/24 h Pr-142 19.2 hr 2.15 MeV
    1.3 Ci/g/sat. Beta Part.
  • [0433]
    [0433]
    TABLE 133
    RADIOACTIVE MICROSPHERES, 600 MICRON SUBSTRATE
    FOR PERMANENT IMPLANTATION INTO TISSUE
    50 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Antimony
    Sb  3.9 Barns 380 mCi/g/week Sb-122 2.74 days 570 KeV Sb-122m
    520 mCi/g/sat. Sb-124m
    Sb-124
    Arsenic
    As  4.2 Barns 430 mCi/g/24 h As-76 26.5 hrs 560 KeV
    920-mCi/g/saturate
    Copper
    Cu  3.0 Barns 270 mCi/g/8 h Cu-64 12.8 hrs 510 KeV Cu-66
    760 mCi/g/sat.
    Lanthanum
    La  8.2 Barns 860 mCi/g/wk La-140 40.2 hr 1600 KeV
    960 mCi/g/sat.
    Tungsten
    W  9.7 Barns 425 mCi/g/wk W-187 24 hr 72-686 KeV W-181
    850 mCi/g/sat. W-185
    Ytterbium-169
    Yb-169 15.4 Barns 180 mCi/g/wk Yb-169 31 d 63-198 KeV Yb-175
    0.55 Ci/g/mo Yb-177
    Lu-177
    Palladium (Enriched)
    Pd  2.7 Barns 290 mCi/g/24 h Pd-109 14 hr 88 KeV Pd-103
    410 mCi/g/satn. Pd-109m
    (Depends upon
    enrichment)
  • [0434]
    [0434]
    TABLE 134
    MULTILAYERED RADIOACTIVE MICROSPHERES, 200 MICRON SUBSTRATE
    FOR TEMPORARY IMPLANTATION INTO TISSUE
    25 MICRON COAT
    ACTIVATION ACTIVITY Ag-11
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Europium
    Eu 3360 Barns 0.31 Ci/g/wk Eu-152 12.4 yr 340-1410 KeV Eu-152m
    1.2 Ci/g/mo Eu-154
    15 Ci/g/yr
    Iridium
    Ir  370 Barns 1.7 Ci/g/wk Ir-192 74 d 316 KeV Ir-194
    6.5 Ci/g/mo
    32 Ci/g/satn.
  • [0435]
    [0435]
    TABLE 135
    MULTILAYERED RADIOACTIVE MICROSPHERES, 600 MICRON SUBSTRATE
    FOR TEMPORARY IMPLANTATION INTO TISSUE
    25 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Enriched Calcium-46
    Ca-46  22 Barns 380 mCi/g/wk Sc-46 84 d 1120 KeV Ca-45
    1.4 Ci/g/mo
    7.9 Ci/g/satn.
    Thulium
    Tm 130 Barns 0.39 Ci/g/wk Tm-170 127 d 7-84 KeV
    1.4 Ci/g/mo
    10 Ci/g/yr
  • [0436]
    [0436]
    TABLE 136
    MULTILAYERED RADIOACTIVE MICROSPHERES, 600 MICRON SUBSTRATE
    FOR TEMPORARY IMPLANTATION INTO TISSUE
    25 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Tantalum
    Ta 19 Barns 60 mCi/g/wk Ta-182 115 d 68-1230 KeV Ta-183
    220 mCi/g/mo
    1400 mCi/g/yr
    Terbium
    Tb 22 Barns 120 mCi/g/wk Tb-160 74.2 d 87-966 KeV
    440 nCi/g/mo
    2200 mCi/g/satn.
  • [0437]
    [0437]
    TABLE 137
    MULTILAYERFD RADIOACTIVE MICROSPHERES, 600 MICRON SUBSTRATE
    FOR TEMPORARY IMPLANTATION INTO TISSUE
    50 MICRON COAT
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Cesium
    Cs 33 Barns  18 mCi/g/wk Cs-134 2.1 yrs 800 KeV Cs-134m
     63 mCi/g/mo
    810 mCi/g/saturate
  • [0438]
    [0438]
    TABLE 128
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS FOR PERMANENT IMPLANTATION
    ACTIVITY
    ACTIVATION PRODUCED OTHER
    CROSS-SECTION BY FLUX FINAL ISOTOPES
    TARGET MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Gold
    Au 98 Barns 6.2 Ci/g/wk Au-198 2.7 d 412 KeV Au-199
    8.0 Ci/g/wk
    Holmium
    Ho 60 Barns 2.7 Ci/g/wk Ho-166 27 hrs 80 KeV
    5.9 Ci/g/satn.
    Lutecium
    Lu 100 Barns 4.3 Ci/g/wk Lu-177 6.7 d 210 KeV Lu-176m
    8.5 Ci/g/mo Yb-169
    9.3 Ci/g/satn. Yb-175
    Praseodymium
    Pr 11.0 Barns 0.75 Ci/g/24 h Pr-142 19.2 hr 2.15 MeV
    1.3 Ci/g/satn. Beta Particle
    Phenium
    Re 44 Barns 2.5 Ci/g/wk Re-186 90 hr 137 KeV Re-188
    3.8 Ci/g/satn.
    Re 43 Barns 2.4 Ci/g/24 hr Re-188 17 hr 155 KeV Pe-186
    3.8 Ci/g/wk
    Samarium
    Sm 37 Barns 1.2 Ci/g/24 hr Sm-153 47 hr 100 KeV Sm-155
    3.5 Ci/g/wk Eu-155
    4.0 Ci/g/satn. Eu-156
  • [0439]
    [0439]
    TABLE 139
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Enriched Calcium-46
    Ca-46 Depends on Sc-47 3.4 d 160 KeV Ca-45
    Enrichment Ca-47
    Ca-49
    Sc-49
    Arsenic
    As 4.2 Barns 430 mCi/g/24 h As-76 26.5 hrs 560 KeV
    920 mCi/g/sat.
    Lanthanum
    La 8.2 Barns 860 mCi/g/wk La-140 40.2 hrs 1600 KeV
    960 mCi/g/satn.
    Tungsten
    W 9.7 Barns 425 mCi/g/wk W-187 24 hr 72-686 KeV W-181
    850 mCi/g/satn. W-185
    Dysprosium
    Dy 790 Barns  57 Ci/g/4 hrs Dy-165 2.35 hrs 95-630 KV Dy-159
    Dy-166
  • [0440]
    [0440]
    TABLE 140
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    50 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Ytterbium-169
    Yb-169 15.4 Barns 180 mCi/g/wk Yb-169 31 d 63-198 KeV Yb-175
    0.55 Ci/g/mo Yb-177
    Lu-177
    Antimony
    Sb 3.9 Barns 280 mCi/g/wk Sb-122 2.74 days 570 KeV Sb-122m
    520 mCi/g/sat. Sb-124m Sb-124
    Bromine
    Br 1.6 Barns 160 mCi/g/24 h Br-82 35.4 hrs 780 KeV Br-80
    310 mCi/g/wk
    330 mCi/g/satn.
    Chromium
    Cr 0.69 Barns 30 mCi/g/wk Cr-51 27.8 d 323 KeV
    95 mCi/g/mo
    210 mCi/g/sat.
    Copper
    Cu 3.0 Barns 270 mCi/g/8 hrs Cu-64 12.8 hrs 510 KeV Cu-66
    760 mCi/g/sat.
  • [0441]
    [0441]
    TABLE 141
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    50 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Gallium
    Ga 2.0 Barns 330 mCi/g/wk Ga-72 14 hrs 835-2510 KeV Ga-70
    480 mCi/g/satn.
    Germanium
    Ge 0.70 Barns   50 mCi/g/wk Ge-71 11 d 92 KeV Ge-75
    120 mCi/g/mo Ge-77
    160 mCi/g/satn. As-77
    Mercury
    Hg 4.5 Barns 350 mCi/g/wk Hg-197 65 hr 77 KeV Hg-199m
    360 mCi/g/satn. Hg-203
    Hg-205
  • [0442]
    [0442]
    TABLE 142
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Palladium
    Pd 2.7 Barns 290 mCi/g/24 h Pd-109 14 hr 88 KeV Pd-103
    410 mCi/g/satn. Pd-109m
    Pd-111
    Ag-111
    Sodium
    Na 0.54 Barns 260 mCi/g/24 h Na-24 15 hr 1370-2750 KeV
    390 mCi/g/satn.
    Yttrium
    Y 1.3 Barns 52 mCi/g/wk Y-90 64.2 hr 2270 KeV
    190 mCi/g/mo Beta Particle
    230 mCi/g/satn.
    Phosphorous
    P 0.19 Barns 25 mCi/g/wk P-32 14.3 d 1.7 MeV
    67 mCi/g/mo Beta only
    100 mCi/g/satn.
  • [0443]
    [0443]
    TABLE 143
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR TEMPORARY REMOVALBE IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Cobalt
    Co  37 Barns 23 mCi/g/wk Co-60 5.26 yr 1.25 KeV
    87 mCi/g/mo
    1060 mCi/g/yr
    Europium
    Eu 360 Barns 0.31 Ci/g/wk Eu-152 12.4 yr 340-1410 Kev
    1.2 Ci/g/mo Eu-152m
    15 Ci/g/yr Eu-154
    Iridium
    Ir 370 Barns 1.7 Ci/g/wk Ir-192 74 d 316 KeV Ir-194
    6.5 Ci/g/mo
    32 Ci/g/satn.
    Enriched Calcium-46
    Ca-46  22 Barns 380 nCi/g/wk Sc-46 84 d 1120 KeV Ca-45
    1.4 Ci/g/mo
    7.9 Ci/g/satn
  • [0444]
    [0444]
    TABLE 144
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR TEMPORARY REMOVALBE IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Thulium
    Tm 130 Barns  0.39 Ci/g/wk Tm-170 127 d 7-84 KeV
    1.4 Ci/g/mo
    10 Ci/g/yr
    Tantalum
    Ta 19 Barns 60 MCi/g/wk Ta-182 115 d 68-1230 KeV Ta-183
    220 mCi/g/mo
    1400 mCi/g/yr
    Terbium
    Tb 22 Barns 120 mCi/g/wk Tb-160 74.2 d  87-966 KeV
    440 mCi/g/mo
    2200 mCi/g/satn.
  • [0445]
    [0445]
    TABLE 145
    RADIOACTIVE MICROFILAMENTS, 150 MICRON DIAMETER
    50 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR TEMPORARY REMOVALBE IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Cesium
    Cs 33 Barns 18 mCi/g/wk Cs-134 2.1 yrs 800 KeV Cs-134m
    63 mCi/g/mo
    810 mCi/g/sat.
    Hafnium
    Hf 2.7 Barns 15 mCi/g/wk Hf-175 70 d 343 KeV Hf-181
    51 mCi/g/mo
    250 mCi/g/satn.
    Hf 3.5 Barns 28 mCi/g/wk Hf-181 45 d 482 KeV Hf-175
    95 mCi/g/mo
    320 mCi/g/satn.
    Indium
    In 2.37 Barns 27 mCi/g/wk In-114m 50 d 190 KeV In-116m
    93 mCi/g/mo In-114
    330 mCi/g/satn.
    Protactinium
    Pa 7.3 Barns 72 mCi/g/wk Pa-233 27.0 d 310 KeV Th prod.
    230 mCi/g/mo
    510 mCi/g/satn.
    Mercury
    Hg 1.13 Barns 7.5 mCi/g/wk Hg-203 47.0 d 279 KeV Hg-197
    26 mCi/g/mo
    91 mCi/g/satn.
  • [0446]
    [0446]
    TABLE 146
    15 MICRON DIAMETER WITH 10 MICRON ACTIVE COAT
    OR 400 MICRON DIAMETER (8-0 SUTURE)
    WITH 10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Dysprosium
    Dy 790 Barns  57 Ci/g/4hrs Dy-165 2.35 hrs 95-630 KV Dy-159
    Dy-166
    Gold
    Au 98 Barns 6.2 Ci/g/wk Au-198 2.7 d 412 KeV Au-199
    8.0 Ci/g/wk
    Holmium
    Ho 60 Barns 2.7 Ci/g/wk Ho-166 27 hrs 80 KeV
    5.9 Ci/g/satn.
    Lutecium
    Lu 100 Barns 4.3 Ci/g/wk Lu-177 6.7 d 210 KeV Lu-176m
    8.5 Ci/g/mo Yb-169
    9.3 Ci/g/satn. Yb-175
  • [0447]
    [0447]
    TABLE 147
    15 MICRON DIAMETER WITH 10 MICRON ACTIVE COAT
    OR 400 MICRON DIAMETER (8-0 SUTURE)
    WITH 10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Rhenium
    Re 44 Barns 2.5 Ci/g/wk Re-186 90 hr 137 KeV Re-188
    3.8 Ci/g/satn.
    Re 43 Burns 2.4 Ci/g/24 hr Re-188 17 hr 155 KeV Re-186
    3.8 Ci/g/wk
    Samarium
    Sm 37 Barns 1.2 Ci/g/24 hr Sm-153 47 hr 100 KeV Sm-155
    3.5 Ci/g/wk Eu-155
    4.0 Ci/g/satn. Eu-156
    Enriched Calcium-46
    Ca-46 Depends on Sc-47 3.4 d 160 KeV Ca-45
    Enrichment Ca-47
    Ca-49
    Sc-49
  • [0448]
    [0448]
    TABLE 148
    15 MICRON DIAMETER WITH 20 MICRON ACTIVE COAT
    OR 300 MICRON DIMETER (9-0 SUTURE)
    WITH 30 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR PERMANENT IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Praseodymium
    Pr 11.0 Barns 0.75 Ci/g/24 h Pr-142 19.2 hr 2.15 MeV
    1.3 Ci/g/satn Beta Particle
    Arsenic
    As 4.2 Barns 430 mCi/g/24 h As-76 26.5 hrs 560 KeV
    920 mCi/g/sat.
    Lanthanum
    La 8.2 Barns 860 mCi/g/wk La-140 40.2 hr 1600 KeV
    960 mCi/g/satn.
    Tungsten
    W 9.7 Barns 425 mCi/g/wk W-187 24 hr 72-686 KeV W-181
    850 mCi/g/satn. W-185
  • [0449]
    [0449]
    TABLE 149
    15 MICRON DIMETER WITH 10 MICRON ACTIVE COAT
    OR 400 MICRON DIAMETER (8-0 SUTURE)
    WITH 10 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR TEMPORARY REMOVALBE IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Cobalt
    Co  37 Barns 23 mCi/g/wk Co-60 5.26 yr 1.25 KeV
    87 mCi/g/mo
    1060 mCi/g/yr
    Europium
    Eu 360 Barns 0.31 Ci/g/wk Eu-152 12.4 yr 340-1410 KeV
    1.2 Ci/g/mo Eu-152m
    15 Ci/g/yr Eu-154
    Iridium
    Ir 370 Barns 1.7 Ci/g/wk Ir-192 74 d 316 KeV Ir-194
    6.5 Ci/g/mo
    32 Ci/g/satn.
    Enriched Calcium-46
    Ca-46  22 Barns 380 mCi/g/wk Sc-46 84 d 1120 KeV Ca-45
    1.4 Ci/g/mo
    7.9 Ci/g/satn
    Thulium
    Tm 130 Barns 0.39 Ci/g/wk Tm-170 127 d 7-84 KeV
    1.4 Ci/g/mo
    10 Ci/g/yr
  • [0450]
    [0450]
    TABLE 150
    15 MICRON DIAMETER WITH 20 MICRON ACTIVE COAT
    OR 300 MICRON DIAMETER (9-0 SUTURE)
    WITH 30 MICRON ACTIVE COAT
    MULTILAYERED RADIOACTIVE MICROFILAMENTS
    FOR TEMPORARY REMOVABLE IMPLANTATION
    ACTIVATION ACTIVITY
    CROSS- PRODUCED OTHER
    TARGET SECTION BY FLUX FINAL ISOTOPES
    MATERIAL (BARNS) 1012/N/CM2/S PRODUCT T-½ ENERGY PRESENT
    Tantalum
    Ta 19 Barns 60 mCi/g/