US 3369121 A
Description (OCR text may contain errors)
Feb. 13, 1968 G. A. BRUNO ET AL 3,369,121
RADIOACTIVE PACKAGE AND CONTAINER THEREFOR Filed April 6, 1966 3 SheetsSheet 1 INVENTORS.' GERALD ,4. BRU/VO THOMAS A. HANEY PAUL NUMEROF KARL RE/NHARDT ATTORNEY Feb. 13, 1968 BRUNO ET AL 3,369,121
RADIOACTIVE PACKAGE AND CONTAXNER THEREFOR Filed April 1966 3 Sheets-Sheet 2 INVENTORS' GERALD A. BRUNO THOMAS A. HANE) PAUL NUMEROF KARL RE/NHARDT ATTORNEY United States Patent Ofifice 3,369,121 RADIOACTIVE PACKAGE AND CONTAINER THEREFOR Gerald A. Bruno, Shrewsbury, Thomas A. Haney, East Brunswick, Paul Numerof, Highland Park, and Karl Reinhardt, Milltown, N..I., assignors to E. R. Squibb & Sons, Inc., New York, N.Y., a corporation of Delaware Filed Apr. 6, 1966, Ser. No. 540,689 Claims. (Cl. 250106) ABSTRACT OF THE DISCLOSURE This invention relates to a new device for containing a column of elutable radioactive material. The device comprises a hollow body, in which the column of radioactive material is contained, closed at its two ends by pierceable closures, preferably made from resilient material. In this manner a closed system is achieved which can be sterilized and remains sterile in use. The device is preferably shipped in a shielding container having a removable closure. The removable closure and the bottom of the container are both apertured so that access can be had to the interior of the container without removing the closure. By use of a closed system consisting of a hypodermic syringe containing the eluting solution, a hypodermic needle therefor that is used to pass through the aperture in the closure and pierce the top of the device so that the solution can be introduced into the top of the column, a tube containing hypodermic needles at both ends, one needle of which is inserted through the aperture in the bottom of the column into the bottom of the device and the other needle through the closure of an empty sealed vial which is also pierced by another hypodermic needle open to the atmosphere through a sterile plug of cotton, a sterile system for eluting the column and recovering the eluate containing the desired radioactive material is achieved. The preferred radioactive material contains the element Mo yielding radioactive technetium as the eluted radioactive material.
This invention relates to packages containing radioactive material and containers therefor and, more particularly, to a package of a sterile column containing a radioactive material and a shielding container therefor and to the sterile column itself.
The use of radioactive isotopes for the diagnosis and treatment of various medical conditions is well known. Unfortunately, however, certain radioactive isotopes have so short a half-life that they cannot be economically shipped from the manufacturer to the attending physician. This has made it necessary for the physician to prepare such isotopes as and where they are to be used. One such isotope is the 99m isotope of technetium which is used for the localization of brain tumors, for example. For a more detailed discussion of the subject, reference is made to an article by Smith in the Journal of Nuclear Medicine, vol. 5, p. 871-882 (1964). This isotope has a half-life of six hours and is obtained as the daughter product of molybdenum M0 It is separated in the form of the pertechnetate ion from M0 absorbed on an alumina column, by elution with dilute hydrochloric acid or saline. Since maximum growth of radioactivity of the Tc occurs in about 23 hours, a column containing Mo may be eluted daily to yield T0 Because of its high radioactivity, such column must be shielded at all times to prevent unnecessary exposure to its radioactivity.
- Prior to this inventinon, such columns were in the form of open ended cylinders and were shipped in shielding containers, made of lead or a lead salt or other material used as a gamma ray shielding agent. In use, such col- 3,369,121 Patented Feb. 13, 1968 umns were either removed from the containers, or, if a container having removable closures on bot-h ends was employed, retained in the container during elution. The eluate was collected in a collecting container, such as a beaker or vial, and had to be sterilized prior to use. This necessitated the sterilization of a radioactive substance thereby increasing both the hazard and difficulty in using such a generator system.
It is an object of this invention, therefore, to provide a novel column for radioactive material, whereby the column can be eluted to yield a sterile, non-pyrogenic radioactive eluate.
It is another object of this invention to provide a novel package containing a novel column for radioactive material enclosed in a radioactive shielding container of such design that the sterile eluate obtained from the column may be removed from the package without removing the column from the container.
These objects are achieved by the columns and containers of this invention, preferred embodiments of which are illustrated in the accompanying drawing wherein:
FIGURE 1 is a perspective view of the separated components that comprise one embodiment of the package of this invention;
FIGURE 2 is an axial section view of the package shown in FIGURE 1, with the components assembled and the package closed;
FIGURE 3 is an elevational view showing the equipment used to load and wash the column of the package of FIGURE 1 of this invention;
FIGURE 4 is a perspective view of the separated components that comprise a second embodiment of the package of this invention; and
FIGURE 5 is an axial section view of the package shown in FIGURE 4, showing the package in use.
Considering the embodiment shown in FIGURES 1, 2 and 3 of the drawings, the package of this invention comprises generally a container having a body 1, a removable top closure 2, and a radioactive column 3 positioned inside the body 1. Since the principal purpose of the container is to store radioactive material, the container is fabricated of lead or other material used as a gamma ray shielding material, such as a lead-antimony alloy iron, or a lead salt, such as lead carbonate or lead sulfide, embedded in plastic. The body 1 is of generally cylindrical shape having a hollow center 4 preferably of circular cross-section and of greater diameter than that of column 3. When the col-umn is placed inside the container, the space between the column and the inner wall of body 11 is preferably filled with a shock absorbant packing material 5, such as corrugated paper, foam plastic or a plastic sleeve.
To permit access through the bottom of the container and limited access through the top of the container, without removing top closure 2, both the bottom wall and the top closure have centrally positioned apertures 6 and 7, sealed by removable plugs 8 and 9, which are also fabricated of gamma shielding materials.
After column 3 has been placed in the body of the container, the container is closed at its top by means of removable closure 2. In the embodiment shown in the drawing, the closure is retained on the body by means of a pair of lugs 10, 10, having enlarged heads 11, 11. The closure 2 is equipped with a pair of arcuate keyhold shaped slots 12, 12, the enlarged openings of which are of greater diameter than are the heads 11. These slots are countersunk so that the outer portions thereof are of suflicient width to accomodate the heads, whereas the inner portions thereof are of width smaller than the heads 11, but of sufficient width to accomodate the shank portions of lugs 10. The closure is also fabricated of lead or other material relatively impervious to radioactivity and,
to insure a tight fit with body 1, the closure is equipped on its inner surface with a circular projection 13 having a circumference slightly less than the circumference of the hollow center.
Although in the preferred embodiment, the closure 2 is retained on the body by means of lugs and keyhole shaped slots, other means may be used to removably connect the closure to the body. Thus, the closure may be simply taped or stapled to the body, or threading may be used.
The column 3 is preferably made principally of glass or a transparent plastic material and is composed of a cylindrical tube 14 closed at its top and bottom by means of stoppers 15 and 16. These stoppers are preferably fabricated of resilient material, such as rubber, that can be pierced by a hypodermic needle, and are held permanently in place by means of a pair of annular aluminum discs 17 and 18 that pass over the outer edges of the stoppers, the sides of the stoppers and are then crimped to the adjacent walls of tube 14, as shown in FIGURE 2. To permit easy access by air to the inside of tube 14, the bottom stopper 16 is equipped with a breather tube 19 that passes through stopper 16 to about half the height of tube 14. So that the outside end of the breather tube 19 is in communication with the atmosphere, (after removal of plug 8,) even when the column 3 is seated in body 1, the bottom stopper 16 is equipped on its outer surface with a groove 20 extending at least from the outer end of breather tube 19 to aperture 6. To assure sterility the breather tube 19 is equipped with a plug 21 of cotton or similar material.
The tube 14 is equipped with a partition 22 which divides the tube 14 into an upper and a lower portion. This partition is preferably integral with the tube 14 along its outer end and tapers downward towards the bottom of tube 14 so as to provide a restricted opening 23 at its lower end. The partition can be and preferably is fabricated of the same material as tube 14. Although the exact position of the partition in tube 14 is not critical, it is preferably positioned in the upper half of tube 14 in such a way that the restricted opening 23 is slightly below the upper end of breather tube 19.
Seated on the upper end of partition 22 is a perforated disc 24 (preferably a glass fritted disc) on which preferably rests a filter pad 25. Resting on top of disc 24, or the filter pad 25, if one is used, is a granulation 26 of a radioactive containing alumina, and optionally also a cation exchange resin, such as Dowex50 8, to prevent passage of the alumina through the tube during elution.
The granulation 26 can be retained in place either by use of a perforated disc (prefereably a cloth disc 27 retained in place by a retaining ring 28), as shown in the drawing, or merely by means of stopper 15.
To prepare the column 3 for use, the granulation 26 is packed into the top portion of the column, the stoppers 15 and 16 are inserted and crimped into place by means of aluminum discs 17 and 18. As shown in FIGURE 3, the top stopper 15 is then pierced by two hollow needles 29 and 30, one of which is connected to a reservoir 31 and the other to a tube 32 open at its other end to the atmosphere. A third hollow needle 33 is inserted through bottom stopper 16 to allow for drainage.
To load the column, the reservoir 31 is filled with a source of radioactivity, such as an aqueous solution of radioactive (M ammonium molybdate, and the solution is permitted to drip through needle 29 onto and through granulation 26. Most of the radioactive molybdenum is adsorbed in the granulation. The excess molybdenum and water pass through the column and are removed through drainage needle 33. The column is then washed with acid and saline to remove any non-adsorbed molybdenum, the needles 29, 30 and 33 are removed, and the column is sterilized, as by autoclaving.
The column 3 is inserted into body 1. The closure 2 is then so positioned over the top of body 1 that the lugs pass through the enlarged portions of slots 9, and rotated 4 to firmly connect the closure to said body. The package is then ready for shipment.
When the package is to be used, the plugs 8 and 9 are removed and the column 3 is then eluted, by injecting a sterile, non-pyrogenic eluting solution, such as sterile, non-pyrogenic isotonic saline, through the top stopper 15 into the upper portion of tube 14. The injection is accomplished by passing the needle of a hypodermic syringe containing the eluting solution through aperture 7 and through stopper 15. The eluate, containing the radioactive material, is collected and maintained in the bottom of tube 14. When the eluate is to be used, it is removed from tube 14 by piercing the stopper 16 with a sterile hypodermic needle (connected to a syringe) by passing the needle through aperture 6 and stopper 16.
Considering now the embodiment shown in FIGURES 4 and 5 of the drawings, the package of this embodiment of the invention differs from the first embodiment primarily in the omission of the lower chamber in the column. It comprises generally a container having a body 101, a removable top closure 102, and a radioactive column 103 positioned inside the body 101. The body 101 and closure 102 are fabricated from gamma ray shielding material as described hereinbefore. The body 101 is of generally cylindrical shape having a hollow center 104 preferably of circular cross-section and of greater diameter than that of column 103. When the column is placed inside the container, the space between the column and the inner wall of body 101 is preferably filled with a shock absorbant packing material 105, such as corrugated paper, foam plastic or a plastic sleeve.
To permit access through the bottom of the container and limited access through the top of the container, without removing top closure 102, both the bottom wall and the top closure have centrally positioned apertures 106 and 107, sealed by removable plugs 10 8 and 109, which are also fabricated of gamma shielding materials.
After column 103 has been placed in the body of the container 101, the container is closed at its top by means of removable closure 102. This may be done by positioning the closure 102 on the container 101 and affixing it by means of a strip of adhesive tape (not shown) or other means. To assure a tight fit, the closure 10-2 is equipped on its inner surface with a circular projection 113 having a circumference slightly less than the circumference of the hollow center.
The column 103 is preferably made principally of glass or a plastic material and is composed of a cylindrical tube 114 closed at its top and bottom by means of stoppers 115 and 116. These stoppers are preferably fabricated of resilient material, such as rubber, that can be pierced by a hypodermic needle and are held permanently in place by means of a pair of annular aluminum discs 117 and 118 that pass over the outer edges of the stoppers, .the sides of the stoppers and are then crimped to the adjacent walls of tube 114, as shown in FIGURE 5.
Positioned in the tube 114, preferably spaced from but near the bottom thereof, is a perforated disc 124 (preferably a glass fritted disc) on which preferably rests a filter pad 1 25. Resting on top of disc 124, or the filter pad 125 if one is used, is a granulation 126 of the same material used in the first embodiment. The granulation 126 can be retained in place either by use of a perforated disc 127, as shown in FIGURES 4 and 5 of the drawing, or merely by means of stopper 115.
The column is prepared for use by the same method used in the first embodiment of this invention, as shown by FIGURE 3. The loaded column 103 is then inserted into body 101 and the closure 102 is positioned over the opening in body 101 and retained thereon by means of an adhesive strip or other means. The package is then ready for shipment.
When the package is to be used, the plugs 108 and 109 are removed and the column 103 is eluted, by injecting a sterile, non-pyrogenic eluting solution, such as sterile, non-pyrogenic isotonic saline, through the top stopper 115 into the upper portion of tube 114. The injection is accomplished by passing the needle of a hypodermic syringe (not shown) containing the eluting solution through aperture 107 and through stopper 115. The eluate, containing the radioactive material, is withdrawn from the bottom of tube 114 by means of a hypodermic needle 34. This needle 34 passes through aperture 106 and bottom stopper 116 into the space between perforated disc 124- and stopper 116. To increase this space, stopper 116 is preferably fabricated to have a concave center portion 35.
The under end of needle 34 is connected through tubing 36 to a second hypodermic needle 37 that passes into a sterile empty vial or other container 38 through a rubber stopper 39 closing the vial and retained thereon by means of a crimped annular aluminum disc 40. To permit the air in the vial to escape as the eluate flows into the vial, the stopper 39 is also pierced by a third hypodermic needle 41, exposed to the atmosphere. To assure sterility of the system, needle 41 is equipped with a plug 42 of cotton or similar material. To minimize the exposure to radiation, vial 38 is retained in a shield 43 of gamma ray shielding material.
In use, the eluate passes from column 103 through needle 34, tubing 36, and needle 37 into vial 38. When the eluate is to be used, it is removed from vial 38 by piercing the stopper 39 with .a'sterile hypodermic needle (connected to a syringe).
Although in both embodiments of this invention, the closures 2 and 102 are designated as top closures, the columns 3 and 103, respectively, can of course be introduced upside down into the body 1 and 1, in which case the top closure becomes a bottom closure.
By use of the packages of this invention it is possible to carry out the entire elution operation under sterile conditions without ever removing the column 3 or 103 from the protective shield, thereby minimizing the possibility of exposure to the relatively high radioactivity of the column. Furthermore, since the whole eluting operation is carried out under sterile conditions, the need to sterilize the radioactive eluate prior to use is obviated.
The invention may be variously otherwise embodied within the scope of the appended claims.
What is claimed is:
1. A column containing a sterile, non-pyrogenic elutable radioactive material to be utilized for diagnosis and treatment of medical conditions, which comprises a hollow portable body, closed at its top and bottom by pierceable autoclavable closures and having positioned therein and spaced from the bottom thereof a source of sterile, non-pyrogenic elutable short-lived medical radioactive material whereby a sterile non-pyrogenic eluate immediately ready for utilization is delivered from the column on elution.
2. The column of claim 1, wherein the pierceable closures are permanently aflixed to said hollow body to seal said body.
3. The column of claim 2 wherein the pierceable closures are fabricated of resilient material.
4. The column of claim 3, wherein the source of the radioactive material contains the element M0 5. The column of claim 3 wherein the pierceable closure at the bottom contains a tube extending through said closure.
6. The column of claim 5 wherein the body is equipped with a hollow partition equipped with means for retaining said source of elutable material on the upper edge of said partition.
7. A package comprising a shielding container and a column containing a sterile non-pyrogenic elutable radioactive material positioned therein; said container having side and bottom Walls, said bottom wall containing a restricted aperture therein; and said column comprising a hollow portable body closed at its top and bottom by pierceable autoclavable closures and having positioned therein and spaced from the bottom thereof a source of sterile, non-pyrogenic elutable short-lived medical radioactive material whereby a sterile non-pyrogenic eluate immediately ready for utilization is delivered from the column on elution.
8. The package of claim 7 wherein the container has a removable closure for the top, said closure having a restricted aperture therein.
9. The package of claim 7, wherein the pierceable closures are fabricated of resilient material and permanently afiixed to said body to seal said body.
10. The package of claim 9, wherein the source of the radioactive material contains the element M0 References Cited UNITED STATES PATENTS 2,682,872 7/1954 Bower 206-6 3.2 X 2,968,721 1/1961 Shapiro et .al. 250-406 X 2,973,758 3/ 1961* :Murrish 206-632. X
ARCHIE R. BOROHELT, Primary Examiner,