US 3746650 A
Description (OCR text may contain errors)
United States Patent 3,746,650 ORGANIC, RADIOISOTOPE-CONTAINING, CAR- BUNACEOUS MATRIX HEATED IN KNERT ATMOSPHERE Thomas N. Lahr, Roseville, and Richard E. Volkmann, Arden Hills, Minn assiguors to Minnesota Mining and Manufacturing Company, St. Paul, Minn. No Drawing. Filed Feb. 26, 1970, Ser. No. 14,683 Int. Cl. Afilr 27/04 U.S. Cl. 252-301.1 R 9 Claims ABSTRACT 0F THE DISCLOSURE The disclosed radioactive source preferably is obtained by heating a particulate ion exchange resin, containing one or more radioisotopes ion-exchanged therein, in an oxygen-free atmosphere. The resulting heat-treated particles contain the radioisotopes non-leachably bound up in a carbonaceous matrix. The heat-treated particles have good chemical and physical integrity and a low inorganic ash content.
This invention relates to radioactive sources of the type wherein the radioactive material is firmly and nonleachably bound within fired particles, each of these particles providing a matrix for the non-leachable retention of the radioactive material. An aspect of this invention relates to methods for producing these radioactive sources.
It has been found that radioactive materials can be non-leachably bound up in carbonaceous matrices which are heat-resistant and mechanically strong. The method of making these radioisotope-containing matrices involves contacting a solution containing radioactive ions with a particulate organic ion-exchange resin for a period of time sufiicient to bring about significant ion exchange, removing the resin from the solution, and heat-treating the resin, which now contains radioactive ions exchanged therein, at a temperature up to about 450 C. The heating step causes shrinking and weight loss, e.g. dehydration, of the resin, which is converted to a carbonaceous, non-ion-exchanging form. The shrinkage, weight loss, and chemical conversion appear to be the reasons for the great physical strength, heat-resistance, and nonleachable entrapment and/0r chemical binding of radioactive material which characterizes these fired (i.e. heattreated) particles. See U.S. Pat. 3,334,050 to Grotenhuis et al., issued Aug. 1, 1967.
The particles disclosed in the 3,334,050 patent are said to be useful in a wide variety of applications, including medical diagnosis and treatment, the manufacture of luminous signs and markers, the elimination of static electricity build-up, and other fields in which a particulate or sheet-like radioactive source is needed. A wide variety of radioisotopes can be used to provide the radioactivity; however, careful selection of radioisotopes is necessary for medical applications, wherein the half-life, specific activity, characteristics of radioactive emission (e.g. wavelength and energy), and the like are extremely critical and variable only within narrow limits. For example, in diagnosis or research techniques using these particles as tracers, the half-life of the radioisotope must be at least a few days, but preferably not more than about 100 days. The radioactive emission from a tracer should preferably consist of electromagnetic radiation, not nuclei or subatomic particles, and the energy and/or wave-length of the electromagnetic radiation and/or the specific activity should be such that the radiation is readily detectible with a sodium iodide crystal radiation counter or an equivalent device.
The term tracer, as used in this application, means a radioactive source introduced into a system such as ice biological system, the radioactivity of the source being monitored thereafter by radiation-sensing equipment, particularly as to its location and intensity. Such tracers are well known in the art of medicine and medical research, which involves studying blood flow and arterialvenous shunting in animals for insight into, for example, mechanisms for cardiovascular disorders.
Certain peculiar problems arise when fired carbonaceous particles containing radioisotopes suitable for tracer work (e.g. blood flow studies) are introduced into biological systems. First, the carbonaceous particles must be sterilized by heating in water or a steam autoclave at 100 C. or, if pressure is used, even higher temperatures. Second, even a slight migration of radioactive material from the carbonaceous particles to the blood (which can act as a leaching medium) or other biological fluid may invalidate the calculations relating to blood flow determinations and interfere with the reproducibility of the experiments. In most non-biological applications, in therapeutic work, and even in some diagnostic work, such calculations are generally not involved. Generally speaking, it is only in certain kinds of tracer work that an extremely high level of experimental precision, accuracy, and reproducibility is necessary. In most fields of application, the radioactive carbonaceous particles produced according to U.S. Pat. 3,334,050 are so resistant to leaching that the minimal amount of radioactive material migrating from the matrix to the leaching medium over a period of hours or days, e.g. considerably less than 1% migration over a period of up to 5 days at room temperature or slightly elevated temperatures (see Examples 1-4 of the 3,334,050 patent) can be considered negligible. It has only recently been observed that the leachability of certain radioisotopes at certain levels of specific activity is subject to hard-to-control variations which impair the validity of blood flow calculations and the like. These variations, though minor, create a quality control problem for the particular manufacturer and an experimental control problem for the researcher. These uncontrolled variations arise in two situations:
(1) when the carbonaceous particles contain more than about 10 or 15 millicuries per gram (mc./g.) of a radioisotope such as Srwhich can form divalent cations, particularly when these particles are subjected both to stringent sterilization procedures and in vivo use, and
(2) when the carbonaceous particles contain certain anionic or other cationic radioisotopes at a very high level of specific activity, e.g. 50 mc./g. or higher.
In the first situation, it has been found that more of the divalent cations may be leached in 20-30 minutes at C. than in several days at room temperature. (Some trivalent cations and some anions, e.g. the yttrium cation or the sulfur-containing anions, are apparently less leachable at almost any temperature.) The amount of divalent cation leached out is small but, nevertheless, unpredictable and uncontrollable enough to be significant in precise, quantitative fields of use such as blood flow studies.
In the second situation, it has been found that it may be necessary to use a specific activity well below 50 mc./ g. to obtain reliable experimental results. Nevertheless, with certain radioisotopes, it is desirable to use particles hav-- ing a specific activity about 50 mc./g. to make it easier to get an accurate radioactivity count with simple, inexpensive radiation-sensing equipment. High specific activities, e.g. 50-100 mc./g., are especially useful when chromium 51 (Cr-51) tracers are used alone or in combination with other tracers. Only 9% of the photons emitted by Cr-Sl are easily-detected high energy gamma rays, the remainder being low energy X-rays. (By way of comparison, Sr-85 emits 100% high energy gamma rays.)
Accordingly, this invention contemplates providing carbonaceous radioisotope-containing particles for use in diagnosis or medical research wherein the particles have been treated so as to make the leachability of the radioisotope more subject to strict quality control, particularly for specific activities above 10 or 15 mc./ g. in the case of divalent, cationic gamma-emitting isotopes and at or above 50 mc./ g. of other isotopes.
This invention also contemplates a process which improves the structural and chemical integrity and reduces the inorganic ash content of these carbonaceous particles.
This invention further contemplates a fired, carbonaceous radioisotope-containing particulate tracer material having a specific activity greater than 10 or 15 mc./g., including specific activities of 50 mc./g. or more, which reliably and predictably retains virtually all of the radioisotope when subjected to leaching media.
Briefly, this invention involves contacting a solution containing radioactive ions with a particulate organic ionexchange resin for a period of time sutficient to bring about significant ion exchange, removing the resin particles from the solution, and heating the particles in an oxygen-free atmosphere at a temperature up to about 450 C. The exclusion of molecular oxygen from the heat-treating atmosphere affects both the physical and chemical structure of the carbonaceous matrix of the particles. The particles are found to contain less oxygen and less inorganic ash, to contain more mole percent hydrogen per mole of carbon, to have greater resistance to attack bystrong reagents such as nitric acid, to be lighter in color, and to be somewhat greater in mean diameter, as opposed to particles fired in air or other oxygen-containing atmospheres. Most important, it appears to make little difference whether the particles of this invention have a specific activity of 5 mc./g. or 100 mc./g.; in either case quality control is surprisingly good, particularly in view of the unusually rigid and exacting standards imposed by the requirements of cardiovascular research practices.
Apparently, the radioisotopes are even more tightly bound and/ or entrapped in the particles of this invention than in similar particles heat-treated in air. It is by no means clear why this improvement is obtained, and this invention is not limited by or dependent upon any particular theoretical explanation. It is well known that heating organic resins in air, even at temperatures below 450- 500 C. can produce oxidation of the resin. Such heating results in weight loss due to dehydration and, perhaps, due to loss of carbon monoxide or carbon dioxide. Blackening of the resin occurs, apparently due to formation of elemental carbon. Fragmenting of polymer chains may also occur. In any event, elemental analyses establish that the heated-in-air resins generally contain a greater mole percent of oxygen and a greater mole percent of carbon (particularly with respect to the relative mole percent of hydrogen), than the unheated resin. Traces of metals introduced during processing of raw resin are converted to inorganic ash upon air firing.
It is to be expected that exclusion of oxygen during heating will result in less oxidation and/ or less carbonization and might result in fewer alterations in the polymer chains of the resins. All of these effects are observed, and, in addition, the shrinkage, weight loss, and inorganic ashing is decreased; the color of the fired particles is not black but may be dark brown or deep amber. What is not expected is that the radioisotopes are even more difiicult to leach from isotope-containing resins fired under vacuum or an oxygen-free atmosphere. It was originally thought that shrinkage of the particulate resin and alterations in the polymer structure aided in non-leachably retaining the radioisotopes, perhaps by some sort of encapsulation and insolubilizing effects, the degraded polymer being, it was found, substantially less soluble than the unheated polymer. However, it now appears that less shrinkage and more retention of the chemical integrity of the polymer (e.g. the C-C and C--H bonds thereof) somehow binds up the radioisotopes more tightly. The resulting less degraded polymer is less soluble in nitric acid; perhaps the polymer fragments resulting from oxidation are easier to attack for some reason, despite their higher oxidation state. It has also been found that heating times can be longer in an oxygen-free system. The striking reduction in inorganic ashing may be due to the retention of relatively larger amounts of organic resinous material. It is theorized that less ashing may also contribute to the structural integrity and strength of the particles of this invention.
The shape of the particles of this invention is essentially the same as that of the particles of the 3,334,050 patent. The average mean diameters tend to be somewhat higher, but spherules or irregularly shaped particles having diameters within the range of 10 to 200 microns can be produced by this invention also. For tracer work, particles made according to this invention should be near the lower end of the preferred size range, e.g. 10-75 microns. Sheetlike radioactive sources can also be produced according to this invention.
The radioisotopes preferred for use in this invention must be capable of existing as an ion in a solvent suitable for ion exchange, e.g. water or buffered aqueous media, lower aliphatic alcohols, lower alkanones, or mixtures of these solvents. These isotopes should have a half life of less than about 100 days and a radioactive decay mechanism which produces high energy photons, photons being preferable to subatomic particles or nuclear debris. At least a few percent of these photons should have a wavelength in the gamma ray region, i.e. about .005 to about 1 angstrom (about .005 to about .1 millimicron). Longer wavelengths are not detrimental so long as more than about 5% of the emission is gamma rays having sufficient energy. The energy of the gamma rays can be as low as about 0.03 million electron volts (mev.), but preferably is 0.15 mev. or higher. Suitable isotopes include chromium 51 (its .32 mev. gamma emission is quite efiicient), strontium (its gamma emission is very useful), niobium 95, scandium 46, ytterbium 169, cerium 141, and non-metallic isotopes such as iodine 125. It is also possible to use SR-90, Tl-204, C14 and the like in this invention, but these materials are not preferred for tracer work due to a long half life and/or a decay mechanism that produces beta particle rather than gama ray emission. Iodine isotopes are particularly well suited for use in the process of this invention, apparently because the oxygen-free atmosphere does not oxidize the trapped ions to molecular iodine, which sublimates rather readily.
Suitable cation exchange resins include any of those disclosed in U.S. Pat. 3,334,050, including the strongly acidic sulfonated polystyrene resins, COOH-containing acrylic resins, phenolic resins containing methylene group-linked sulfonic groups, etc. Suitable anion exchange resins include polystyrene resins containing quaternary ammonium groups, etc.
The atmosphere duringthe heating step must be substantially free of molecular oxygen. For example, the furnace or oven can be evacuated or the air can be flushed out with a current of nitrogen, as is well known in the art. It is sometimes convenient to place the particles in a container which is then placed in the oven or furnace. This container can be evacuated or flushed with nitrogen in any suitable manner, and if the container is suificiently well sealed, the evacuation or flushing of the oven itself may be unnecessary. The preferred method is to introduce a constant flow of nitrogen (e.g. 0.5 to 2 liters/min.) into the heating chamber of the oven or furnace. A crucible containing air-dried, isotope-containing (but unheated) particles is placed in the chamber. The door of the chamber is closed, but not tightly sealed, thus permitting efilux of the flushed air. The heating step is then begun. Other non-oxidizing gaseous atmospheres besides nitrogen can be used in the heating step, e.g. helium, argon, neon, their cogeners, or mixtures of these with themselves or with nitrogen. A suitable type of heat source is, for example, the electric resistance heating element of an ordinary electric furnace. The particles should be solvent free during the heating step, which generally takes about an hour to reach the desired temperature and lasts for about 2-20, preferably 4-16 hours at that temperature. The desired temperature is generally at least 200 C. (preferably at least 250 C.) but, given the present state of the ionic exchange resin art, never significantly greater than about 450 C., since all known ion exchange resins undergo extensive decomposition at temperatures near 500 C.
EXAMPLE 1 Part A: Introduction of radioisotope by ion exchange A solution of 25 ml. of dilute HCl containing mo. of Sr-85 as SrCl was agitated with 5 grams of spherical resinous beads (Dowex SOWXS") -30 microns in diameter. The untreated beads (i.e. before ion exchange) consisted of a strongly acidic cation exchange resin of the sulfonated polystyrene type, more particularly a polymer containing C H SO repeating units of the formula -CH -CH(SO )-CH wherein is a benzene ring. The untreated beads contained no detectable amount of any metallic element. After the completion of the ion exchange step, the beads were removed from the column and air dried.
Part B: Heat treatments under nitrogen The beads obtained in Part A were placed in a crucible, which was placed in the heating chamber of an oven. A conduit supplied nitrogen at the rate of 1.0 liter/min. to the heating chamber. The door of the chamber was closed and the oven was heated up to a temperature of 380 C. over a period of an hour. Even before the oven reached this temperature, the atmosphere in the heating chamber was substantially entirely nitrogen. The oven was held at this temperature for 8 hours. The fired (heat treated) beads were cooled and found to have a specific gravity of 15 mc./g.
Elemental analysis of the organic portion of the fired beads indicated an empirical formula of C H SO Part C: Other heat treatments Identical beads treated in accordance with Part A were fired as in Part B except that the nitrogen flushing step was omitted. The organic portion of the resulting fired beads had the empirical formula C H SO The organic portion of beads made according to Part A but fired in an evacuated oven were found to have the empirical formula C H SO The air fired beads appeared to contain quinone or hydroquinone-like nuclei which probably resulted from oxidation of the benzene rings. Both the nitrogen and vacuum fired beads appeared to have lost sulfur monoxide and sulfur dioxide during the firing since two out of three benzene rings lacked sulfonyl radicals.
None of the fired beads, regardless of whether the firing was under vacuum, nitrogen, or air, was free of inorganic ash. However, the ash content of the nitrogen-fired beads was only 0.6 wt. percent of the total bead material compared to 13.6 wt. percent for the air-fired beads. The vacuum fired beads contained 1.8 wt. percent inorganic ash.
In soak tests, samples of beads obtained according to Parts A and B of this example were soaked in 0.9 Wt. percent aqueous sodium chloride solution for a period of 25 minutes at slightly above 100 C. and greater than atmospheric pressure, a very stringent soak test, more severe than prolonged leaching at room temperature. The supernatant solution was measured for radioactivity with a conventional scintillation counter. A minimum standard limit of 0.1% migration of the total isotope activity was selected as being realistic in relation to even the most se- EXAMPLE 2 The procedure of Example 1(A) and (B) was followed using (Jr-51 in the 50 ml. of water instead of Sr-85. Several samples of nitrogen-fired beads Were obtained, the amounts of Cr-Sl and the beads being regulated so that some samples of beads contained .50 mc./g. and some contained 75 mc./g. High temperature soak tests indicated that the quality control with Cr-51 compared favorably with the Sr-SS samples.
As the person skilled in the art will readily understand from the foregoing disclosure, the exclusion of oxygen gas from the heating chamber or other closed heating system appears to have a tendency to preserve the carbon-carbon or, in any event, the carbon-hydrogen bonds of the ion exchange resin. Analytical evidence indicates that the number of moles of carbon per mole of hydrogen in the isotope-containing resin heat-treated according to this invention is increased by a factor less than 2, as compared to the unheated resin. Heating in air, on the other hand, appears to increase this C/ H molar ratio by a factor of more than 2, as compared to the unheated resin. For example, in column 3 of the 3,334,050 patent it is stated that the 'C/H Weight percent ratio is initially 48.3/5.1, a molar ra tio of about 0.821. The fired C/H Wt. percent ratio is 67.5 :3.0, a molar ratio of about 19:1. The particles of Example 1 of this invention have an initial C/H molar ratio of 1:1 and a nitrogen-fired C/H molar ratio of about 1.311.
What is claimed is: 1. A method for the production of radioactive sources which comprises the steps of:
contacting a liquid medium containing ratioactive ions with an organic ion exchange resin until the amount of ion exchange which has occurred is sufi icient to provide said ion exchange resin with a level of specific activity of at least 10 millicuries per gram,
heating said ion exchange resin at a temperature within the range of about 200 to about 450 C. in a closed system,
substantially excluding oxygen gas from said closed system at least prior to the time said ion exchange resin reaches a temperature of 200 C. and begins to be converted to a substantially non-ion-exchanging form.
2. A method according to claim wherein said ion exchange resin is particulate.
3. A method according to claim 1 wherein oxygen gas is substantially excluded from said closed system by flushing the air from said closed system with a current of nitrogen gas.
4. A method according to claim 1 wherein oxygen gas is substantially excluded from said closed system by evacuating the air therefrom.
5. A method according to claim 1 wherein the exclusion of oxygen by said excluding step is sufiicient to provide a relatively lower ash content in the non-ion-exchanging form of the ion exchange resin, as compared to an air-fired ion exchange resin containing the same amount of the same radioisotope subjected to the same amount of heat, and wherein said radioactive ion is a divalent cation.
6. A method according to claim 11 wherein the exclusion of oxygen by said excluding step is sufiicient to provide a non-ion-exchanging form of the ion exchange resin which is characterized by an organic carbonaceous matrix having a carbon-to-hydrogen molar ratio which is no more than twice the carbon-to-hydrogen molar ratio of the said ion exchange resin prior to said heating.
7. A method accordingrto claim 1 wherein said ion exchange resin is air dried prior to said heating step.
8. In a method for producing a radioactive source from an ion exchange resin containing radioactive ions in which the resin is contacted with the ions, removed, and converted to a substantially non-ion exchanging form, and wherein said non-ion exchanging form of said resin has a level of specific activity of at least 10 millicuries per gram, the improvement which comprises:
heating said ion exchange resin at a temperature in the range of about 200 to about 450 C. in a closed system free of oxygen gas until said ion exchange resin is no longer capable of further ion exchange.
9. A heat treated radioactive particle produced according to the method of claim 2, said particle having a carbon-to-hydrogen molar ratio less than twice the carbon-tohydrogen molar ratio of the unheated particle.
References Cited UNITED STATES PATENTS CARL D. QUARFORTH, Primary Examiner R. L. TATE, Assistant Examiner US. Cl. X.R. 4241 UNITED STATES PATENT canon CERTEFECATE 0E CGEEEQTEON Patent No. 3, 7 46 650 Dated July 17 1973 Inventor(s) Thomas N. Lahr and Richard E. Volkman'n It is certified that error appears in the above-identified p'atent and that said Letters Patent. are hereby corrected as shown below:
Column 2, line 5, after "search" change the comma to a period and insert the following:
- They are particularly useful in cardiovascular research, and
line 7,, change "for" to of Column 3, line 8, change "of" to for so it reads "for other isotopes".
Column 4, line 33, change "@005" to .0005 so it reads (about .0005 to about .1 millimicron).
line U3, change "SR-90" to Sr-9O Column 5, line &2 (under Part B of Example 1), change '.'specific gravity" to'-- specific activity Column 6, line 5 4 (in Claim 2), after "claim' insert 1 so it reads according to claim 1 Signed and sealed this 25th day of December 1973.
EDWARD M.FLETCHER,JR. RENE D. TEGTMEYER Attesting Officer Acting Commissioner of Patents FORM PO-105O (10'69) USCOMM-DC 60376-969 u.s GOVERNMENT Pnnumc OFFICE. I969 0-466-334