PROCESS FOR THE PURIFICATION OF GA-68 FROM ELUATE DERIVING FROM 68GE/68GA GENERATORS AND CHROMATOGRAPHIC COLUMNS FOR USE IN SAID PROCESS

Abstract

Chromatography columns for the purification of eluates from .sup.68Ge/.sup.68Ga generators comprising silica as stationary phase and purification processes that use said columns are described.

Claims

1-10. (canceled)

11. Process for the preparation of a radiopharmaceutical containing Ga-68 wherein a solution of eluates from 68Ge/68Ga generators is passed through a column for chromatography purification comprising a stationary phase of silica having a granulometry inferior to 100 micron and thereafter said solution is directly poured in a container containing the labeling kit.

12. Process according to claim 11 wherein: a chromatography column for purifying 68Ga from 68Ge comprising a stationary phase made of silica having a granulometry inferior to 100 micron is placed in line at the exit of a .sup.68Ga/.sup.68Ga generator; the solution from the generator is passed though the column; the purified solution containing 68Ga collected from the column is directly added into a container containing the labeling kit.

13. A radiopharmaceutical kit comprising the radioactive isotope .sup.68Ga produced through the process according to claim 11.

14. A radiopharmaceutical kit comprising the radioactive isotope .sup.68Ga produced through the process according to claim 12.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0023] The process according to the invention allows in one step the trapping of the Ge-68 that needs to be eliminated from the eluate in output from the generator and thus directly use the solution of Ga-68 deriving from the generator for the reconstitution of the labeling kit without further treatment or steps.

[0024] The process according to the invention, by allowing the direct trapping of the Ge-68 while the eluate flows from the generator to the container containing the labeling kit as described above, allows widening the spread of Ga-68 similarly to what happens with the Tc-99m.

[0025] In order to achieve the above, the process according to the present invention uses a column comprising a suitable stationary phase which, placed at the generator output line, acts as a trap for the Ge-68.

[0026] In fact, it was surprisingly found that silica is capable of exerting the dual action of trapping the Ge-68 and letting the Ga68 freely pass simultaneously with the passage of the eluate of the generator without needing washing and elution steps, which prevents complicating or prolonging the labeling procedure, allowing an effective purification at the same time as the addition of the eluate to the kit.

[0027] It should be noted that, although silica is well known as stationary phase for chromatographic purifications, it has never been used for the trapping of Ge-68 in the radionuclidic purification of eluates from Ge-68/Ga-68 generators nor it could be expected to exercise the dual action as described above on the components of the eluate deriving from a .sup.68Ge/.sup.68Ga generator and on the other hand, other materials commonly used as stationary phase for chromatographic purification columns were not capable of carrying out the same action.

[0028] In particular, in order to be effective in the process according to the invention, the silica must have granulometry not higher than 250 microns, preferably less than 100 microns. Optimal results were obtained with silica having granulometry of less than 50 microns, preferably comprised between 20 e 10 microns.

[0029] This type of silica can therefore be used for the preparation of the chromatographic columns to be used in the process according to the invention directly connected to a .sup.68Ge/.sup.68Ga generator according to the standard preparation techniques used in the field.

[0030] In particular, according to the invention, disposable columns may be prepared in which the amount of silica is between 2 g and 200 mg. Said columns are placed at the output of the generator to purify the solution of Ga-68 from Ge-68.

[0031] By passing the radioactive solution eluted from a Ge-68/Ga-68 generator through the column thus prepared, only a negligible amount of Ga-68 remains retained in the column while almost all of the Ge-68 remains trapped, thus allowing an eluate to be obtained which fully meets the needs of purity required by the regulations for the labeling kits with Ga68.

[0032] It should be noted that the column according to the invention retains the Ge-68 present in the eluate as is, without the need to change the pH or the composition, so as to allow directly recovering a purified solution of Ga-68 avoiding intermediate dilution, concentration and/or transfer steps. The entrapment of Ge-68 by a simple passage on a dedicated cartridge does not complicate or prolong the labeling procedures, providing a radionuclidic purification along with the elution of the generator.

[0033] It should be noted that the use of such a cartridge offers the possibility to prepare a kit that allows the labeling with Ga-68 by the direct addition of the eluate deriving from the generator to the substrate to be labeled, without any other accessory operation.

Example 1

[0034] Purification of a Solution of Ga-68 in HCl 0.1 N

[0035] 10 empty plastic columns provided with polyethylene partitions were charged with 650 mg of pharmaceutical grade silica with granulometry of 20-10 microns.

[0036] The cartridges thus obtained were used without any washing or pre-conditioning in 10 elution tests of a Ge-68/Ga-68 generator based on TiO2.

[0037] Each column was connected to the output of the generator and the solution of Ga-68 obtained by eluting the generator with 5 ml of HCl 0.1 N was directly collected in a bottle.

[0038] The activity of Ga-68 in the eluate and in the cartridge was measured immediately while the samples were left to decay for 2 days before measuring the content of Ge-68 by HP-Ge gamma spectrometry.

[0039] In the 10 tests, the average activity of Ga-68 retained by the columns was 3% while the activity of Ge-68 retained was on average 90% of the total amount released by the generator.

Example 2

[0040] Purification of a Solution of Ga-68 in HCl 0.05 N

[0041] 10 empty plastic columns provided with polyethylene partitions were charged with 650 mg of pharmaceutical grade silica with granulometry of 20-10 microns.

[0042] The resulting cartridges were used without any washing or pre-conditioning in 10 elution tests of a Ge-68/Ga-68 generator based on organic resin.

[0043] Each column was connected to the output of the generator and the solution of Ga-68 obtained by eluting the generator with 5 ml of HCl 0.05 N was directly collected in a bottle.

[0044] The activity of Ga-68 in the eluate and in the cartridge was measured immediately while the samples were left to decay for 2 days before measuring the content of Ge-68 by HP-Ge gamma spectrometry.

[0045] In the 10 tests, the average activity of Ga-68 retained by the columns was 4% while the activity of Ge-68 retained was on average 95% of the total amount released by the generator.