US 3561932 A
Abstract available in
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Description (OCR text may contain errors)
Feb. 9, 1971 RUV ET AL 3,561,932
INDIUM GENERATOR Filed Jan 26, 1967 1 I I I F I G. 3
n a. a a a F l G. 4
INVENTORS IRWIN J. GRUVERMAN BYGREGORY G ROCCO 0% 9%amd0z W F I G. 2
ATTORNEYS United States Patent 3,561,932 INDIUM GENERATOR Irwin J. Gruverman, Needham, and Gregory G. Rocco,
Wakefield, Mass., assignors to New England Nuclear Corporation, Boston, Mass., a corporation of Massachusetts Filed Jan. 26, 1967, Ser. No. 611,963 Int. Cl. B01d 11/02; C01g 15/00, 19/00 US. Cl. 23-312 4 Claims ABSTRACT OF THE DISCLOSURE A generator of a daughter radionuclide, particularly radioactive indium (ln and a method of loading a particulate substrate of the generator with a parent radionuclide. The daughter radionuclide, which results from the radioactive decay of its parent, is selectively extracted from the substrate by a mineral acid solvent (eluant), such as hydrochloric acid (HCl) at a concentration less than one-tenth normal (0.1 N).
An appropriate substrate is of zirconium oxide (ZrO in two layers of different granularity. Flow of the extractive eluant through the substrate is regulated by a flow distribution cap, which also holds the substrate in place within the generator, and by various porous layers intermediate to the substrate and at its extremities to prevent drying of the substrate, thus, avoiding channelled flow of the eluant.
The substrate is loaded by depositing the parent radionuclide in the form of radioactive tin (Su as by percolation with an aqueous solution of hydrochloric acid and tin at a normality between 0.1 and 1.0; washing the substrate; and repeating the foregoing set of steps, using, for each succeeding set of steps, the percolating eflluent used in the immediately preceding set of steps.
BACKGROUND OF THE INVENTION The present invention relates to the generation of radioactive indium (particularly In especially for medical and industrial scanning and tracing, using radioactive tin (Su over a wide range of specific activity as a precursor radionuclide from which In is generated by radioactive decay.
Radioactive indium in the form of I11 has certain advantages over other radioactive scanning and tracing agents, such as T0 I Hg and Hg For example, from a medical standpoint, the delivered radiation dosage to a patient is much lower using ln than when using I Hg or Hg while at the same time In achieves scanning resolution comparable or superior to these other nuclides. As compared with Tc In has the advantage of a shorter half life, i.e. 1.7 hours as compared with 6.0 hours for Te This shorter half life, together with the fact that In radiates no beta particles, for example as compared with I .and Hg decreases patient radiation dosage. Also, the shorter half life simplifies decontamination procedures in the laboratory and hospital and permits radiotracer procedures to be performed on the patient after a shorter decay interval than is the case for any of the above mentioned radionuclides. Further, with respect to the generator itself, this short half life permits more frequent elution of the In from the generator, as compared for example with Tc since the rate at which the daughter (In in one case, and Tc in the other case) is generated from the parent is controlled primarily by the half life of the daughter.
Although, because of the lack of beta particles and the short half life of In relative to 1 radiation dosage to the patient is decreased, nevertheless, In has an advantage over other replacements for I in that it emits gamma rays which can be scanned using the same conven tional equipment used for I This is true because the principal gamma ray energy of I is 364 kev. and that of In is 390 kev. By contrast, the gamma ray energy of Tc is kev. and requires the use of substantially different collimation components of the scanning equipment.
The post-elution chemical procedures for treating the eluted daughter to prepare the final scanning agents are generally simpler for In than they are for Tc Not only does In offer the aforesaid advantages but, in addition, an Su -In generator system is highly desirable because Sn has a relatively long half life of 118 days compared with 67 hours for Mo from which Tc is generated. A long parent half life is desirable, firstly, because the longer the parent half life, the longer the useful life of the generator, and secondly, because production and delivery of the generator can be carried out on a more convenient schedule. Thus, with a shorter lived parent, shipping and delivery schedules must be closely observed, with resulting higher costs, to make sure that delays are minimized. Furthermore, a shorter lived generator must be prepared to order, whereas a long lived generator can be prepared conveniently for stock.
All of these advantages make an Su -In generator highly desirable.
Although there have been attempts to provide a commercially useful Sn -In generator system, until the present invention no one has successfully done so.
in order to understand the problems involved in providing such a system, it is necessary to explain the principles of a parent-daughter radionuclide generator of this type. In the conventional form of such a generator, the parent radionuclide is deposited or fixed on a solid particulate substrate, e.g. alumina, zirconium oxide, organic ion exchange resins, etc., in the form of a column. The parent is a radionuclide having a relatively long half life and decaying to the daughter which has a relatively short half life, this relatively short half life being one of its desirable properties as a radioactive scanning agent, but at the same time making its storage and shipment diificult. In effect, with the aforesaid generator system, the shelf life of the daughter becomes that of the parent since it is available as long as the parent is available. When it is desired to use the daughter, it is extracted or eluted from the generator column by passing a solvent, selective to the daughter, through the column. The eluting solvent must have the property of efficient removal of the daughter from the generating column without removal of any significant fraction of the parent. The daughter continues to be generated in the column as long as the parent remains.
There were a number of major problems in achieving a commercially satisfactory Sn ln generator. Firstly, Sn is a costly material and must be utilized eificiently in loading the generator in order for cost of the generator to be commercially acceptable. Secondly, difficulty was met in achieving satisfactorily high yields of In in the eluting fluid without substantial leakage of the parent Sn i.e. without the eluting fluid containing unacceptable amounts of the Su Such leakage renders the generator unaceptable because the product eluate contains the long lived impurity, Su thereby making it more dangerous for medical use as well as shortening the life of the generator. Thirdly, difliculties were met in depositing or fixing on the substrate column a sufficient mass of tin to achieve adequate Sn intensities. Fourthly, difficulties were met in preventing channeling of the eluting solution through the column, which is undesirable because only a fraction of the column capacity is achieved resulting in low elution yields and reduced tin retention capacity. Fifthly, difficulties were met in preventing the column from drying between elutions with consequent inconsistencies in elution flow rate and elution etficiencies. Sixthly, difliculties were met in reducing the concentration of dissolved substrate matter in the eluant to acceptable levels. Post elution chemistry is complicated by the presence of such substrate material.
The present invention provides for the first time a commercially acceptable Sn In generator system and method which overcomes all the aforesaid difiiculties.
SUMMARY OF THE INVENTION According to one aspect of the present invention, high In yields are achieved in the eluting fluid with minimum leakage of Sn and substrate material, to thereby solve these problems, by using as an eluting fluid, with a zirconium oxide substrate material, an aqueous solution of HCl at a concentration of less than 0.1 N, and preferably between about 0.02 N and 0.08 N. The most preferred HCl concentration is from about 0.04 N to 0.06 N. Optimum results have been achieved with an HCl concentration of 0.05 N. Although other acids, particularly mineral acids, such as HNO and HBr can be used in place of HCl, the latter is highly preferred.
Also, according to another aspect of the present invention, the Su is loaded on the particulate substrate, particularly ZrO to produce the In generator by the steps of 1) contacting the substrate particles with an Sn solution to deposit Su on such particles, (2) separating the solution from the particles (preferably steps (1) and (2) are carried out by flowing the solution through a column of the substrate particles), (3) then Washing the particles (preferably by passing a wash solu tion through the column) and (4) repeating these steps at least once, but preferably twice, using as the Sn solution in each repeat of step (1) the spent separated Sn solution from the preceding treatment with Sn solution, to thereby overcome the aforesaid loading difficulty and the aforesaid difiiculty of achieving adequate Su column intensities. Preferably, the Sn is in an aqueous HCl solution having a normality of less than 1.0 and more than 0.1, preferably, between 0.3 and 0.5, and which has been treated with an oxidizing agent, preferably by bubbling chlorine gas through it, and the wash solution is an aqueous HCl solution between 0.02 N and 0.08 N, preferably 0.04 N to 0.06 N.
Also, according to a further aspect of the invention, the generator comprises two layers of the particulate substrate, preferably zirconium oxide particles, the upper layer being relatively coarse and the lower layer relatively fine. These layers are separated by a porous, liquid-retaining layer of an inert material, preferably glass Wool, having pores small enough to retain the eluting liquid. The upper coarse layer is covered with a similar liquidretaining layer and the entire assembly is secured within the column container at its bottom by a porous support secured to the container and at its top by a cap secured in the container and having perforations distributed over Sn solution to deposite Sn on each particles, (2) sepdiificulties of channeling due to drying of the coarse substrate and due to nonuniform flow over the column crosssectional area, are overcome.
The objects and advantages of the invention will be apparent from the following description and the accompanying drawings of an illustrative embodiment of the invention:
BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:
FIG, 1 is an elevational view in section of a radionuclide generator embodying the invention;
FIG. 2 is a horizontal sectional View along the section line Z-2 of FIG. 1 showing a top view of a flow distribution cap;
FIG. 3 is a perspective view of the flow distribution cap shown in FIG. 2;
FIG. 4 is a partial sectional and perspective view of a composite assembly including the generator of FIG. 1 and a shield for the generator.
DESCRIPTION OF THE PREFERRED EMBODIMENTS With reference to the drawings, a generator 10 embodying the present invention is constituted of a hollow cylinder 20 of durable and chemically inert composition, desirably glass, which incorporates a radionuclide generator column 30. The cylinder 20 extends from an outwardly flared portion 21 to a constricted portion 22 taking the form of a spout.
The generator column 30 includes two substrate layers 31 and 32 which are supported by a porous supporting layer 40. The substrate layers 31 and 32 are desirably particles of zirconium oxide (ZrO with the upper layer 31 being composed of coarser particles than the lower layer 32. The porous support layer 40 is of durable and chemically inert composition, being advantageously of fritted glass which is sealed to the inside wall of the cylinder 20.
Disposed between the two substrate layers 31 and 32 is an intermediate layer 33 of porous and inert material such as glass wool. At the top of the generator column 30 is a further layer 34 of porous and inert material such as glass wool. The column 30 is held in place against the support layer 40 by a flow distribution cap 50, which is chemically inert with respect to the substances used in conjunction with the generator 10, At the same time the cap 50 is flexible so that it will grip the interior wall of the cylinder 20. Plastic has been found to be a suitable material for the cap 50, which is detailed in FIGS. 2 and 3.
In order to produce the desired daughter radionuclide in the form of radioactive indium (In the substrate layers 31 and 32 are loaded with the corresponding parent radionuclide in the form of radioactive tin (Sn The parent decays naturally into its daughter, which is removed from the column 30 by selective extraction with a suitable solvent, i.e. eluant. In the case of In such a solvent is hydrochloric acid with a normality of less than 0.1 N.
The elution is accomplished using conventional attachments and accessories for the generator 10 by gravity flow or by forced flow of the eluant through the generator 10. By having the upper substrate layer 31 of greater coarseness than the lower layer 32, the efficiency of the elution process is enhanced. Since the upper layer 31 is coarser than the lower layer 32, there is less resistance to flow through the upper layer 31. Gravity flow encounters less resistance in the coarse layer 31 than in the fine layer 32. However, the pressure head is greater in the fine layer. The result is that uniformity of flow through the overall column is promoted. The fine layer 32 also serves to filter particles originating in the coarse layer. Alternatively, elution may take place by forcing the eluant upward through the spout 22 into the column 30 and out of the flared portion 21. Again, elution takes place using conventional accessories.
The eluting fluid wets the substrate during elution. If the residual moisture of the substrate varies during the various inter-elution intervals, there is a consequent effect upon the rate of flow of the eluant and upon the efficiency of elution. Flow takes place with greater rapidity, and hence greater eluting efficiency, to the extent that the substrate is wet rather than dry. In addition, the rate of flow is more uniform for each elution if significant loss of moisture from the substrate is prevented during inter-elution intervals. Furthermore, nonuniform drying of the columnar substrate can lead to preferred channels of flow for the eluant. The result is not only ineflicient use of the substrate but also the possibility of a breakdown by which traces of the parent Sn are removed from the column in the eluate containing the desired daughter In The orous layers 33 and 34 of the column 30 serve to reduce variations in the amount of moisture retained by the substrate, as well as promote uniformity of. flow. To that end both layers 33 an 34 are of a porosity which is suitable for the retention of suflicient moisture to maintain a satisfactory degree of moistness in the generating column 30. The intermediate layer 33 reduces the drainage of moisture from the upper substrate layer 31. It also curtails evaporation from the lower substrate layer 32. Similarly, the upper porous layer 34 curtails the evaporation of moisture from the upper substrate layer 31.
In addition, when eluant enters the porous layers 33 and 34, it spreads over the cross section of the generator column 30. The uniform distribution of eluant over the cross section of the columnar substrate plays a significant role in avoiding channelling and in promoting uniformity of flow. Uniformity of eluant flow through the generator column 30 is also promoted by the configuration of the flow distribution cap 50, details of which are set forth in FIGS. 2 and 3.
The retaining cap 50 has an aperture 51 at its center and notches 52 in its periphery. For the particular embodiment shown in the perspective view of FIG. 3 there are four uniformly distributed circumferential notches 521 through 5 2-4, which extend radially inward along the base of the cap 50. In addition, the periphery of the cap 50 extends upwardly into a compressible resilient rim 53 which frictionally engages the inside wall of the glass container 20, as shown in FIG. 1, to secure the cap and the layers of particulate zirconium oxide and glass wool within the generator cylinder 20.
In order for the generator of FIG. 1 to function efficiently, its substrate layers are advantageously loaded with a significant mass of Sn In accordance with the invention, a method of loading the substrate layers includes the steps of contacting the substrate particles, as
by percolation, with a solution containing radioactive tin in order to deposit the parent radionuclide. Once the parent has been deposited upon the substrate particles the flow of depositing solution is terminated, following which the particles are washed by a wash solution in order to remove any residual excess of radioactive tin. The foregoing set of steps is repeated at least once, using for each repetition the contacting tin solution effluent from the preceding set of steps. By using the tin solution effiuent a number of times, an adequate loading of the substrate with the parent radionuclide is established cumulatively at a considerable cost saving, as compared with the use of a fresh contacting solution with each set of steps.
In a tested model of the invention, the radioactive tin of the contacting solution was in aqueous solution of hydrochloric acid which had been treated by bubbling chlorine gas through it. The normality of the tin solution ranged from less than 1.0 N to more than 0.1 N, with a preferred range between 0.3 N and 0.5 N. The wash solution was an aqueous solution of hydrochloric acid of normality less than 0.1 N, desirably between 0.02 N and 0.08 N, and preferably in the range from 0.04 N to 0.06 N.
For a typical and illustrative column 30 of the generator 10 in FIG. 1, the diameter is approximately 1 inch. In such a column, the coarse substrate layer 31 preferably ranges in height from inch to 2 inches, with particles ranging in size from 50 to 100 mesh, as sold and marketed under the designation Bio-Rad HZO-l Ion Exchange Crystals. The fine substrate layer .32 preferably ranges in height from A; inch to inch and is composed of particles ranging from 100 to 200 mesh. In general, the heights of the various substrate layers 31 and 32, for a column of prescribed diameter, depend in part upon the extent to which the column is to be loaded with the parent radionuclide.
In an illustrative column 30 with a diameter of approximately 1 inch, the porous layers 33 and 34 preferably range in thickness from approximately /5 to A of an inch and are desirably of wettable borosilicate fibers in the range from 0.0002 to 0.0003 inch. Such glass wool fibers are commonly available under the designation Corning Number 3950. To achieve suitable porosity for the layers 33 and 34 ranging in thickness from approximately /s to A of an inch, the mass of the borosilicate fibers advantageously corresponds to a weight in the range from 200 to 300 milligrams. Suitable porosity for the layers 33 and 34 can also be achieved using such Wettable materials as filter cloth and the like.
For a tested model of the invention, the glass support layer was constructed as an integral part of the cylinder 20 and was of a character commonly designated in the glass blowing art as coarse fit. The thickness of a tested frit layer 40 was slightly in excess of A of an inch, being desirably in the range from A to of an inch.
In an illustrative model of the invention, the flow distribution cap had a thickness of approximately of an inch. The cap is advantageously of any of the common plastics, such as polyethylene, which provide suitable adhesion to the sides of the cylinder 20 in order to provide a friction fit by which the constituents of the generator column 30 are retained in place. In one design of the cap 50 the apertures of 52-1 through 52-4 and the central aperture 51 were symmetrically arranged and disposed so that approximately /2 of the cap area was open to the passage of the eluting fluid.
The generator cylinder 20 may be of a suitable plastic,
such as polyethylene. However, the cylinder 20 is advantageously of relatively non-porous and inert material such as glass, in which event, it is frangible, and precautions must be taken to prevent breakage. In any case, it is desirable to protect the cylinder 20 since the generator column 30 contains radioactive materials when loaded. Accordingly, the cylinder is desirably mounted in a flexible protective shield as shown in FIG. 4. A suitable shield is of plastic which secures the cylinder 20 by having the rim of its flared portion 21 resting on the top edge of the shield and by having a soft plastic Wedge 61 with the shield and encircling the cylinder 20 near the spout 22. In a test model of the invention, the shield 60' was illustratively about 7 inches in length and about 1 /2 inches in outside diameter, while the cylinder 20' contained by the shield was approximately 1 inch in diameter. In use, the plastic shielded generator 10 of FIG. 4 is generally employed in conjunction with radiation shielding, such as provided by a lead closure or by a leadshielded chamber. However, where the radioactivity of the column 30 is at a suitably low level, the generator 10 may be employed without such auxiliary shielding.
Other adaptations of the invention, and techniques of employment, will occur to those skilled in the art.
1. In a method of eluting In from a column consisting of particles of Zr0 substrate upon which Sn is supported, the improvement comprising eluting said In by passing through said column an aqueous solution of hydrochloric acid at a concentration below 0.1 N but not less than about 0.02 N, whereby high In yields are achieved With minimum leakage of $11 and zirconium originating in the zirconium substrate.
2. A method according to claim 1, said concentration of HCl being between 0.02 N and 0.08 N.
3. A method according to claim 1, said concentration of HCl being between 0204 N and 0.06 N.
4. A method according to claim 1, said column being enclosed in a plastic container.
References Cited UNITED STATES PATENTS 8 OTHER REFERENCES Mayer et al.: Ind. and Eng. Chem, vol. 52, N0. 12, December 1960, pp. 993 to 994.
Gillette: ORNL-3802, May 1965, pp. 1 to 3, 8, 9, 11, 12, 14,18, 19.
NORMAN YUDKOFF, Primary Examiner S. J. EMERY, Assistant Examiner U.S. Cl. X.R.