WO1997001852A1

WO1997001852A1 - Technetium-99m generators

Info

Publication number: WO1997001852A1
Application number: PCT/US1996/010553
Authority: WO
Inventors: Petrus C. Vermeeren; Robert G. Wolfangel
Original assignee: Mallinckrodt Medical, Inc.
Priority date: 1995-06-28
Filing date: 1996-06-25
Publication date: 1997-01-16

Abstract

A miniaturized technetium-99m generator that provides significant advantages over the prior art generators is provided. The generator comprises an elutable container including a substantially insoluble gel comprised of a metallic cation associated with fission molybdenum-99 in a ratio of at least 1:1. The container has a height not greater than 0.75 inches and a diameter not greater than 0.4 inches which can be manufactured and shipped in a cost-effective manner while remaining light weight and well shielded and providing high specific activity technetium-99m.

Description

TECHNETTUM-99M GENERATORS

Field of the Invention This invention relates to technetium-99m generators and more particularly to such a generator that uses fission-produced molybdenum-99 combined with a gel-like matrix to provide high specific activity technetium- 99m in a miniature-sized generator.

Background of the Invention

Technetium-99m is a radionuclide that is used extensively in diagnostic nuclear medicine applications. It is obtamed as a decay product of its parent radionuclide, molybdenum-99, and has a half-life of about 6 hours. Therefore, to provide technetium-99m on demand, devices referred to as generators have been developed and are commercially available. These devices typically comprise a chromatographic column filled with a matrix onto which the molybdenum-99 is adsorbed and the technetium-99m that forms due to decay is separated and removed by elution of the column with an eluant, such as saline. In most commercially available technetium-99m generators, the molybdenum-99 is adsorbed to an aluminum oxide matrix.

The molybdenum-99 used in a generator may be produced by either fission of highly enriched U-235 targets or by neutron bombardment (n,γ) of natural Mo-98 targets. The Mo-99 produced from the U-235 targets, referred to as "fission Mo-99", has very high specific activity and permits a generator of about 1.5 inches in height and 0.5 inches in diameter to be constructed. The Mo-99 produced by neutron bombardment, referred to as "neutron Mo-99", has a significantly lower specific activity and requires a significantly larger alumina column having a height of about 3 inches and a diameter of about 1 inch. Although having a much lower specific activity, neutron Mo-99 has a significant advantage in favor of its use in that its production does not produce large amounts of gaseous and solid radioactive waste materials, as does the fission Mo-99 production process. Because of the low specific activity of the neutron Mo-99, however, a generator using neutron Mo-99 requires a relatively large volume of eluant to elute a diagnostically effective amount of Tc-99m. This results in an undesirably low concentration of the eluted Tc-99m. Commercially available generators, whether using fission Mo-99 or neutron Mo-99, require at least a 1 inch lead shield surrounding the generator. As a result, even the more compact fission Mo-99 generators can weigh up to about 50 pounds. The costs associated with preparing the containers that hold and shield the generator and shipping the generator are significant and affect the ultimate cost of the generator to the consumer.

In U.S. Patent No. 5,382,388, Ehrhardt et al. describe a process for preparing a radionuclide generator that utilizes neutron Mo-99 associated with a zirconyl cation to form a zirconyl-molybdenate gel that is used as the matrix for the generator. This process permits a relatively compact generator (about the same size as commercially available fission Mo-99 generators) to be provided with relatively high specific activity while using the relatively waste- free neutron Mo-99. For commercial purposes, however, this type of generator still requires significant lead shielding and is costly to produce and ship. Therefore, a need continues to exist in the field of radionuclide generators for an efficient, cost-effective generator that provides high specific activity Tc-99m, and is both relatively light weight and well-shielded. Summary of the Invention

The present invention is directed to a miniaturized technetium-99m generator that provides significant advantages over the prior art generators. The generator comprises an elutable container including a substantially insoluble gel comprised of a metallic cation complexed with fission molybdenum-99 in a ratio of at least 1:1. The container has a height not greater than 0.75 inches and a diameter not greater than 0.4 inches which can be manufactured and shipped in a cost-effective manner.

Among the many objects and advantages of the present invention may be noted the provision of a Tc-99m generator that requires less lead shielding and is therefore less costly to manufacture and ship than currently available generators, the provision of such a generator that provides high specific activity Tc-99m in a small volume of eluant, and the provision of such a generator that requires less auxiliary shielding at the preparation and administration site.

Detailed Description of the Preferred Embodiments

It has been discovered that fission Mo-99 can be advantageously complexed with a metallic cation to form a substantially insoluble gel that is suitable for use as the matrix for a Tc-99m generator. The resulting generator is of a compact size that requires less lead shielding than presently available generators and is therefore lighter, easier to handle, less costly to ship, less costly to package, and requires less auxiliary shielding at the site of its ultimate use. Moreover, the generator of the present invention yields high specific activity Tc-99m in a small volume of eluant, about 0.25ml to about 1.0ml, which can be conveniently handled by the individual formulating and administrating the resulting radiopharmaceutical.

The substantially insoluble gel for use as the matrix in the generator of the present invention comprises a metallic cation, such as zirconium, tantalum, polonium, platinum, niobium, hafnium, titanium, cerium, tin, and barium, and mixtures thereof, forming the substantially insoluble gel complexed with the fission Mo-99. The matrix may be prepared essentially by the method described in U.S. Patent No. 5,382,388 or U.S. Patent No. 4,280,053, the entirety of each being hereby incorporated by reference hereto, except that fission Mo- 99 is used in place of the neutron Mo-99 disclosed therein. Briefly, according to the method described in U.S. Patent No. 5,382,388, a substantially clear solution containing the metallic cation and the fission Mo-99 is provided where the metallic cation is present as a component of a dissolved complex of the metallic cation and a complexing agent and the fission Mo-99 is present in the solution as a component of a dissolved complex of the Mo-99 and a complexing agent. The dissolved complexes are decomposed to form a slurry containing a precipitate of the metallic cation which is collected for use as the matrix in the generator. According to the method described in U.S. Patent No. 4,280,053, the matrix is prepared by dissolving neutron Mo-99 in a slight excess of aqueous ammonia or sodium hydroxide solution and acid is added to adjust the pH to between 1.5 and 7. The resultant solution is added to a stirred aqueous solution of a metallic cation and a molybdate precipitate is formed. The precipitate is collected , air-dried and then sized for use in a generator. In either of the above methods, the preferred metallic cation is zirconium. The amounts of the metallic cation solution and the molybdenum solution are combined such that the gel that is formed contains approximately a 1:1 ratio of metallic cation to total molybdenum. A slight excess of the metallic cation is preferred. The resulting metallic cation-molybdate gel is dried and poured into a glass column suitable for use in a Tc-99m generator. If desired, a "bed" of alumina or hydrous zirconium oxide may first be placed in the column to act as a final scavenger for any molybdate which may be released from the gel. Typically, the bottom seals and needle (outlet) are already in place. After pouring in the gel, the top rubber seal, aluminum seal, and inlet needle are put in place and the column put in a generator "shell" containing an appropriate reservoir of saline or water eluant and plumbing valves, hoses, etc. Typically, the column is washed with several volumes of eluant to remove any soluble molybdate and any fine particles. After a suitable period, the generator is ready for use.

Suitable elutable containers include, for example, a glass column such as those used in standard chromatography which is then encased in a shell including appropriate lead shielding, associated plumbing and a reservoir of eluant, to form a generator assembly.

In accordance with the present invention, the Tc-99m generator column preferably has a capacity ranging from 0.05-0.25ml and requires only 50-250mg of the metallic cation/fission Mo-99 matrix (δ=lg/ml). The fission Mo-99 can be produced at a specific activity of >10,000 Ci/gram and a standard 1-2 Curie generator column containing volumes as low as 0.01-0.02 ml may be constructed.

As various changes could be made in the above compositions and processes without departing from the scope of the invention, it is intended that all matter contained in the above description be interpreted as illustrative and not in a limiting sense.

Claims

What is claimed is:

1. A radionuclide generator for technetium-99m comprising an elutable container including a substantially insoluble gel comprised of a metallic cation associated with fission molybdenum-99 in a ratio of at least 1:1, the container having a height not greater than 0.75 inches and a diameter not greater than 0.4 inches.

2. The radionuclide generator of claim 1 wherein the metallic cation is zirconyl.

3. The radionuclide generator of claim 2 further comprising a layer of alumina or hydrous zirconium oxide at the bottom of the container.