SYSTEM AND METHOD OF RECOVERING A PARENT RADIONUCLIDE FROM A RADIONUCLIDE GENERATOR

Abstract

A method for recovering a parent radionuclide from a radionuclide generator is disclosed where the parent radionuclide is adsorbed to a stationary phase. The method contains a series of elutions. At least one elution is with an alcohol. At least one elution with water. At least one elution is with a mineral acid other than hydrochloric acid that is paused to soak the stationary phase with the mineral acid.

Claims

1. A method for recovering a parent radionuclide from a radionuclide generator, the radionuclide generator comprising the parent radionuclide adsorbed to a stationary phase, the method comprising a series of elutions comprising: at least one elution with an alcohol; at least one elution with a mineral acid; and at least one elution with water; where the at least one elution with a mineral acid is paused to soak the stationary phase with the mineral acid, and the mineral acid does not comprise hydrochloric acid.

2. A method for recovering a parent radionuclide from a radionuclide generator comprising the parent radionuclide adsorbed to a stationary phase, the method comprising: (i) eluting the stationary phase with an alcohol one or more times to obtain an alcohol eluate; (ii) eluting the stationary phase with a mineral acid one or more times to obtain a mineral acid eluate; (iii) eluting the stationary phase with water one or more times to obtain an aqueous eluate; (iv) isolating the parent radionuclide, from the alcohol eluate obtained in step (i), the mineral acid eluate obtained in step (ii) and the aqueous eluate obtained in step (iii); where step (ii) comprises pausing the one or more mineral acid elution to soak the stationary phase with the mineral acid, and the mineral acid does not comprise hydrochloric acid.

3. A parent radionuclide recovered according to the method of claim 1.

4. A method for recycling a parent radionuclide from a first radionuclide generator for reuse in a second radionuclide generator, the method comprising, (i) providing a first radionuclide generator, the radionuclide generator comprising the parent radionuclide adsorbed to a stationary phase; (ii) eluting the stationary phase of the first radionuclide generator with an alcohol one or more times to obtain an alcohol eluate; (iii) eluting the stationary phase of the first radionuclide generator with a mineral acid one or more times to obtain a mineral acid eluate; (iv) eluting the stationary phase of the first radionuclide generator with water one or more times to obtain an aqueous eluate; (v) isolating the parent radionuclide from the alcohol eluate obtained in step (ii), the mineral acid eluate obtained in step (iii) and the aqueous eluate obtained in step (iv); (vi) loading the isolated parent radionuclide into the second radionuclide generator, such that the parent radionuclide is adsorbed to a stationary phase of the second radionuclide generator; where step (ii) comprises pausing the one or more mineral acid elution to soak the stationary phase with the mineral acid, and the mineral acid does not comprise hydrochloric acid.

5. The method of claim 1, wherein the mineral acid comprises an acid other than hydrochloric acid.

6. The method of claim 1, wherein the stationary phase is soaked with the mineral acid for about 12 hours or more.

7. The method of claim 1, wherein the stationary phase is soaked with the mineral acid for about 24 hours or more, about 36 hours or more, about 48 hours or more, about 72 hours or more, between about 12-50 hours, between about 20-55 hours, between about 20-50 hours, between about 12-24 hours, between about 15-24 hours, between about 20-25 hours.

8. The method of claim 1, wherein the alcohol is methanol.

9. The method of claim 1, wherein the water is ultrapure water (e.g. milli Q) or deionized water.

10. The method of claim 1, wherein the parent radionuclide is germanium-68 (Ge-68)

11. The method of claim 1, wherein the radionuclide generator is a germanium-68/gallium-68 (Ge-68/Ga-68) generator.

12. The method of claim 1, wherein the mineral acid is a concentrated mineral acid.

13. The method of claim 1, wherein the mineral acid comprises one or more hydrogen halide acid.

14. The method of claim 1, wherein the hydrogen halide acid is hydroiodic acid and/or hydrobromic acid.

15. The method of claim 1, wherein the hydroiodic acid has a strength of at least about 40%, at least about 50%, about 50-60%, preferably about 57%.

16. The method of claim 1, wherein the hydrobromic acid has a strength of at least about 30%, at least about 40%, about 40-50%, preferably about 48%.

17. The method of claim 1, wherein the alcohol elution step comprises a single elution.

18. The method of claim 1, wherein the mineral acid elution step comprises multiple elutions with mineral acid, at least 2 elutions, at least 3, at least 4.

19. The method of claim 1, wherein the step of eluting with water is carried out after each mineral acid elution.

20. The method of claim 1, wherein the step of eluting with water is carried out after each of the one or more mineral acid elutions in step (ii).

21. The method of claim 1, wherein the step of eluting with water is carried out after each of the one or more mineral acid elutions in step (iii).

22. The method of claim 1, wherein the parent radionuclide is isolated using liquid-liquid extraction.

23. The method of claim 1, wherein the parent radionuclide is extracted using a chlorinated organic solvent, such as carbon tetrachloride, chloroform, dichloroethane, dichloromethane, aromatic solvents such as benzene or toluene, preferably chloroform.

24. The method of claim 1, wherein the method optionally comprises repeating one or more of steps (i)-(iii).

25. The method of claim 1, wherein the method optionally comprises repeating one or more of steps (ii)-(iv).

26. The method of claim 1, wherein the stationary phase is an ion exchange resin.

27. The method of claim 1, wherein the generator is a chromatography column

28. The method of claim 1, wherein the stationary phase comprises a silica matrix, such as octadecyl silica resin (C-18).

29. The method of claim 1, wherein the stationary phase comprises an organic chelating group bound to the silica matrix for retaining the parent nuclide.

30. The method of claim 1, wherein the organic chelating group comprises laurylgallate.

31. The method of claim 1, wherein the organic chelating group consists of laurylgallate.

32. The method of claim 1, wherein the chemical purity of the recovered parent radionuclide is at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0032] These and other features of the invention will become more apparent from the following description in which reference is made to the appended drawings wherein:

[0033] FIG. 1 is a schematic of the methods of recovering a parent radionuclide according to an embodiment of the present invention;

[0034] FIG. 2 is a graph showing yield of Ge-68 as a function of number of elutions performed for methods of recovery according to an embodiment of the present invention. The elution regimes for Rounds 1-6 are described in Tables 1-6 below; and

[0035] FIGS. 3A-F show the yield of Ge-68 recovered after each elution in Rounds 1-6, categorized by elution type in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION

[0036] The term “radionuclide” refers to an atom with excess nuclear energy making it unstable and that undergoes radioactive decay. Radionuclides are also known as radioactive nuclides, radioisotopes or radioactive isotopes. Radioactive decay may produce a new stable nuclide, or a new unstable radionuclide, which may undergo further decay. The term “parent radionuclide” in the context of the present invention refers to a radionuclide that decays into a new radionuclide, or “daughter radionuclide”. Examples of parent radionuclides and their daughter radionuclides include Mo-99/Tc-99m, Ge-68/Ga-68 and W-188/Re-188.

[0037] The term “radionuclide complex” refers to any compound or salt comprising the radionuclide. In the methods of the present invention, the parent radionuclide may be present in the eluates as a radionuclide complex. For example, the parent radionuclide may elute bound to part of the stationary phase (e.g. .sup.68Ge-laurylgallate, .sup.68Ge-silica), or may react with the mineral acid and elute as a new complex (e.g. .sup.68GeCl.sub.4, .sup.68GeI.sub.4). The radionuclide complexes obtained from elution with HI and Br, i.e. GeI.sub.4 (melting point 144° C.) and GeBr.sub.4 (melting point 26° C. and boiling point 186° C.), are stable at room temperature and non-volatile. The parent radionuclide may be isolated as a radionuclide complex which may be used directly for loading into a new radionuclide generator.

[0038] The term “radionuclide generator” refers to a system containing a parent radionuclide which decays into a daughter radionuclide, where the half-life of the parent is longer than the half-life of the daughter. The decay of the parent to the daughter is continuous and the daughter radionuclide can be extracted repeatedly. Radionuclide generators typically comprise an ion exchange column in which the parent radionuclide is bound (adsorbed) to a stationary phase in the column. The daughter radionuclide can be obtained by eluting the stationary phase with a mobile phase to release the daughter radionuclide from the stationary phase. The radionuclide generator may be partially depleted. By partially depleted, it is meant that the parent radionuclide has undergone decay, but the generator is not completely exhausted of activity.

[0039] Common stationary phases for radionuclide generators include oxidic substrates such as silica (SiO.sub.2), alumina (Al.sub.2O.sub.3), zirconia (ZrO.sub.2), titanium oxide (TiO.sub.2), tin oxide (SnO.sub.2), tantalum oxide (Ta.sub.2O.sub.5), vanadium oxide (V.sub.2O.sub.5) and niobium oxide (Nb.sub.2O.sub.3). Common mobile phases for eluting daughter radionuclides from the stationary phase include hydrogen chloride (HCl) and saline.

[0040] The terms “elution”, “eluting”, “eluent” and “eluate” are known in the art. Elution and eluting refers to the process of washing or rinsing the stationary phase with a mobile phase to extract or separate a substance or material from the stationary phase. “An elution” refers to a single wash or rinse of the stationary phase with the mobile phase. The “eluent” is the mobile phase that the stationary phase is washed with and the resulting solution containing the extracted substance and the mobile phase which is obtained from the elution or eluting is the “eluate”.

[0041] Pausing an elution to increase the contact time between the eluent and the stationary phase is also known in the art. When an elution is paused, discharge of the eluent is prevented such that the eluent remains in contact with the stationary phase. In other words, the stationary phase is soaked with the eluent. The “soak time” or “contact time” in the context of the invention refers to the amount of time that the eluent (e.g. mineral acid) is in contact with the stationary phase when an elution is paused. The “total soak time” refers to the sum of the soak times of each of the one or more elutions.

[0042] The term “concentrated” in the context of “concentrated acid” or “concentrated mineral acid” refers to the maximum concentration of an acid in an aqueous solution, or within 10% of the maximum % concentration. For example, the maximum concentration of HCl owing to its solubility in water is around 38%. The maximum concentration of HI is around 57%. The maximum concentration of HBr is around 48%. The term “diluted” in the context of “dilute acid” refers to an acid concentration below the maximum concentration, or a concentration lower than 10% below the maximum percentage concentration.

[0043] The term “elution regime” in the context of the recovery methods of the present invention refers to the series of elutions carried out on the stationary phase of a radionuclide generator. A schematic of the fundamental elution regime according to the invention is shown in FIG. 1. The line arrows indicate the order in which the elutions may be carried out and the block arrows indicate recovery of the parent radionuclide. In general, the elution regime starts with an alcohol elution (1) and is followed by one or more mineral acid elution (2). Each mineral acid elution is paused in order to soak the stationary phase with the mineral acid. Each mineral acid elution is followed by a water elution (3). The parent radionuclide is then isolated from the alcohol eluate (1a) obtained from the alcohol elution(s) (1), the mineral acid eluate (2a) obtained from the mineral acid elution(s) (2), and the aqueous eluate (3a) obtained from the water elution(s) (3).

[0044] The term “laurylgallate”, otherwise known as dodecyl gallate or Dodecyl 3,4,5-trihydroxybenzoate, refers to the chemical compound having formula C.sub.19H.sub.30O.sub.5.

[0045] The term “chemical purity” can be defined as the proportion (e.g. percentage) of the desired chemical or compound in a sample.

[0046] The term “radiochemical purity” refers to the amount of total radioactivity in a sample which is present as the desired radionuclide.

[0047] In the context of the present invention, “yield” of the parent radionuclide refers to the amount of parent radionuclide recovered compared to the total amount of parent radionuclide present in the generator. The yield of the radionuclide can be measured in terms of radioactivity e.g. in becquerels (Bq).

[0048] The term “isolating” in the context of isolating the parent radionuclide as described in the present invention refers to separating or extracting the parent radionuclide from a matrix (e.g. an alcohol, mineral acid or aqueous eluate). Isolation (extraction) techniques include, but are not limited to, liquid-liquid extraction and solid-phase extraction. The Applicant has developed an efficient liquid-liquid extraction for mineral acid and aqueous eluates containing a parent radionuclide using chlorinated organic solvents such as chloroform. The parent radionuclide extracts can then be dissolved in dilute HCl (e.g. 0.001N-1N) ready for loading into a new generator. However, the isolation (extraction) method may also be performed by replacing chloroform with any other chlorinated hydrocarbon that is non-miscible with aqueous solvents, for example, carbon tetrachloride (CCl.sub.4) or dichloromethane (CH.sub.2Cl.sub.2). The extraction can also be performed with other non-water miscible organic phases in which the germanium halides are soluble, for example, benzene, toluene, carbon disulfide.

[0049] The use of the word “a” or “an” when used herein in conjunction with the term “comprising” may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one” and “one or more than one.” Any element expressed in the singular form also encompasses its plural form. Any element expressed in the plural form also encompasses its singular form. The term “plurality” as used herein means more than one, for example, two or more, three or more, four or more, and the like.

[0050] As used herein, the terms “comprising,” “having,” “including” and “containing,” and grammatical variations thereof, are inclusive or open-ended and do not exclude additional, un-recited elements and/or method steps. The term “consisting essentially of” when used herein in connection with a composition, use or method, denotes that additional elements, method steps or both additional elements and method steps may be present, but that these additions do not materially affect the manner in which the recited composition, method or use functions. The term “consisting of” when used herein in connection with a composition, use or method, excludes the presence of additional elements and/or method steps. A use or method described herein as comprising certain elements and/or steps may also, in certain embodiments consist essentially of those elements and/or steps, and in other embodiments consist of those elements and/or steps, whether or not these embodiments are specifically referred to.

[0051] As used herein, the terms “about” or “around”, when used to describe a recited value, means within 10% of the recited value, unless otherwise stated.

[0052] The present invention will be further illustrated in the following examples.

EXAMPLE 1

Recovery of Ge-68 Using Alcohol and HCl

[0053] Partially depleted Ge-68/Ga-68 generator columns were obtained for preliminary testing. A series of elutions with ethanol and dilute hydrochloric acid (up to 6N) were performed. It was found that it was not possible to use hydrochloric acid of concentrations above 6N due to the formation of highly volatile .sup.68GeCl.sub.4 (boiling point 84° C.).

[0054] Recovery yields of Ge-68 in the order of 50-70% were achieved. It was found that the generator column became clogged easily, preventing efficient elution.

EXAMPLE 2

Recovery of Ge-68 Using Alcohol and HI/HBr

Column Preparation

[0055] Ge-68/Ga-68 generator columns were obtained from ITG (ITM Isotopen Technologien Munchen AG). The generator column specifications were as follows—column material: silica gel modified with laurylgallate (CAS: 166-52-5); primary package: PEEK column; secondary package: lead containers; lead shielding: 36-50 mm thickness; shelf life: 12 months or 250 elutions; eluent for obtaining daughter Ga68: sterile 0.05 M aqueous hydrochloric acid solution; nominal Ge-68 activity at manufacture 0.3 GBq-2 GBq. The generator columns selected for testing had a range of ages (see Table 3).

[0056] The generator columns were dried and any residual hydrochloric acid was removed by flowing pressurized air through the column.

Elution of Ge-68

[0057] The elution regimes and acid soak times as carried out on the generators tested are shown in Tables 1-6 below.

[0058] The elutions were carried out as follows. The column was eluted with methanol (10-20 mL) at room temperature and the methanol eluate collected. Elutions with concentrated hydroiodic acid (57%) and/or hydrobromic acid (48%) (4-15 mL) at room temperature were performed and each acid elution was followed by elution with milli Q (MQ) water (10-20 mL) at ˜100° C. The mineral acid and aqueous eluates were collected. During each elution with hydroiodic acid and/or hydrobromic acid, the elution was paused halfway so that the column remained in contact with the acid (soaking) for the indicated time period. The elution regime of methanol, and hydroiodic acid/hydrobromic acid followed by a water flush was repeated as necessary.

Elution Regimes

[0059]

TABLE-US-00001 TABLE 1 Round 1 elution regime Elution Volume (ml) Activity Recovered (MBq) Soak Time (Hrs) Me[OH] 1 10 11.85 Me[OH] 2 10 8.24 Me[OH] 3 15 17.26 Me[OH] 4 15 9.23 Me[OH] 5 15 1.99 Me[OH] 6 15 0.68 Me[OH] 7 15 0.354 Me[OH] 8 15 0.528 Me[OH] 9 15 0.704 MQ H.sub.2O 1 15 5.25 HBr 1 15 8.05 1.7 MQ H.sub.2O 2 15 4.54 HBr 2 15 0.695 1.8 HBr 3 15 0.12 1.3 MQ H.sub.2O 3 15 2.23 HBr4 10 0.783 0.5 MQ H.sub.2O 4 10 2.06 HBr 5 10 0.379 0.7 MQ H.sub.2O 5 10 0.885 HBr 6 10 0.27 0.8 MQ H.sub.2O 6 10 0.813 MQ H.sub.2O 7 10 0.371 Me[OH] 10 15 0.858 Me[OH] 11 15 0.286 Me[OH] 12 15 0.168 MQ H.sub.2O 8 15 0.532 HBr 7 15 1.25 0.7 MQ H.sub.2O 9 15 6.01 HBr 8 15 1.692 0.8 MQ H.sub.2O 10 15 5.2 Me[OH] 13 20 0.109 MQ H.sub.2O 11 15 0.649 HI 1 15 0.963 0.9 MQ H.sub.2O 12 20 30.4 HI 2 20 1.502 0.6 MQ H.sub.2O 13 15 9.98 Me[OH] 14 15 1.803 MQ H.sub.2O 14 20 7.48 HI 3 15 0.654 1.0 MQ H.sub.2O 15 15 1.951 MQ H.sub.2O 16 15 9.43 MQ H.sub.2O 17 15 4.41 Me[OH] 15 15 1.436 MQ H.sub.2O 18 15 1.433 HI 4 15 0.374 0.9 MQ H.sub.2O 19 15 6.9 MQ H.sub.2O 20 15 3.75 Me[OH] 16 10 0.97 MQ H.sub.2O 21 15 1.426 HI 5 15 0.328 0.7 MQ H.sub.2O 22 15 3.09 HI 6 15 0.439 0.6 MQ H.sub.2O 23 15 2.67 MQ H.sub.2O 24 15 1.56 MQ H.sub.2O 25 10 0.329 Me[OH] 17 10 0.37 HI 7 10 0.027 0.8 MQ H.sub.2O 26 15 2.4 Me[OH] 18 10 0.244 HI 8 15 0.028 0.7 MQ H.sub.2O 27 15 2.31 HI 9 10 0.422 0.5 MQ H.sub.2O 28 15 1.708 MQ H.sub.2O 29 10 0.17 Me[OH] 19 15 0.073 MQ H.sub.2O 30 10 0.912 HBr 9 10 0.057 0.7 MQ H.sub.2O 31 15 0.743 HI 10 10 0.07 0.7 MQ H.sub.2O 32 15 1.571

TABLE-US-00002 TABLE 2 Round 2 elution regime Elution Volume (ml) Activity Recovered (MBq) Soak Time (hrs) Me[OH] 1 20 0.36 MQ H.sub.2O 1 15 8.03 MQ H.sub.2O 2 15 0.029 MQ H.sub.2O 3 15 0.03 Me[OH] 2 20 202 Syringe Rinse 15 22.6 (H.sub.2O) 1 Syringe Rinse 15 1.491 (H.sub.2O) 2 Me[OH] 3 15 17.71 Me[OH] 4 15 2.97 Me[OH] 5 15 0.501 MQ H.sub.2O 4 15 0.565 HI 1 15 20.4 19.3 MQ H.sub.2O 5 15 83.4 MQ H.sub.2O 6 15 32.5 Me[OH] 6 15 7.68 MQ H.sub.2O 7 15 2.72 HI 2 15 2.28 1.3 MQ H.sub.2O 8 15 7.99 MQ H.sub.2O 9 15 14.1 Me[OH] 7 15 4.41 MQ H.sub.2O 10 15 1.887 HI 3 15 1.115 19.0 MQ H.sub.2O 11 15 20.4 MQ H.sub.2O 12 15 6.31 Me[OH] 8 10 1.506 MQ H.sub.2O 13 15 0.727 HI 4 10 0.521 19.5 MQ H.sub.2O 14 10 3.64 MQ H.sub.2O 15 10 13.36 HI 5 10 0.225 1.8 MQ H.sub.2O 16 10 1.99 MQ H.sub.2O 17 10 0.502 MQ H.sub.2O 18 10 1.057 MQ H.sub.2O 19 10 0.746 MQ H.sub.2O 20 10 0.629

TABLE-US-00003 TABLE 3 Round 3 elution regime Eluent Volume (ml) Activity (MBq) Soak Time (Hrs) Water 10 8.8 Me[OH] 1 10 11.78 Me[OH]2 10 4.44 Me[OH] 3 10 1.961 Me[OH] 4 10 4.6 Me[OH] 5 10 1.045 MQ H.sub.2O 1 40 1.754 HI 1 10 3.42 1.7 MQ H.sub.2O 2 10 10.85 MQ H.sub.2O 3 10 20.2 MQ H.sub.2O 4 10 7.57 MQ H.sub.2O 5 10 4.38 HI 2 10 0.538 76.9 MQ H.sub.2O 6 10 20.4 MQ H.sub.2O 7 10 4.1 Me[OH] 6 10 1.208 MQ H.sub.2O 8 10 1.725 HI 3 10 0.531 71.9 MQ H.sub.2O 9 20 7.485 MQ H.sub.2O 10 20 0.932 MQ H.sub.2O 11 20 0.1 HI 4 10 0.25 18.7 MQ H.sub.2O 12 20 2.33 MQ H.sub.2O 13 20 0.25 MQ H.sub.2O 14 20 0.358

TABLE-US-00004 TABLE 4 Round 4 elution regime Eluent Volume Activity Recovered (MBq) Soak Time (Hrs) Me[OH] 1 20 38.1 Me[OH] 2 20 2.01 Me[OH] 3 20 0.616 MQ H.sub.2O 1 20 126.865 HI 1 10 259 21.7 MQ H.sub.2O 2 20 621 HI 2 10 26.8 22.8 MQ H.sub.2O 3 20 106.2 HI 3 10 7.45 69.7 MQ H.sub.2O 4 20 70.2 HI 4 10 6.58 0.7 MQ H.sub.2O 5 20 24.6 MQ H.sub.2O 6 10 15.12

TABLE-US-00005 TABLE 5 Round 5 elution regime Eluent Volume Activity Recovered (MBq) Soak Time (Hrs) Me[OH] 1 20 41.3 MQ H.sub.2O 1 20 0.15 HI 1 10 10.28 23.0 MQ H.sub.2O 2 20 432 HI 2 10 17.79 4.0 MQ H.sub.2O 3 20 218 HI 3 10 8.93 18.6 MQ H.sub.2O 4 20 177 HI 4 10 7.04 3.2 MQ H.sub.2O 5 20 107.3 HI 5 10 3.78 18.6 MQ H.sub.2O 6 20 89.5 HI 6 10 3.17 4.2 MQ H.sub.2O 7 20 52.8 HI 7 10 2.09 18.8 MQ H.sub.2O 8 20 42.7 HI 8 10 2.16 3.0 MQ H.sub.2O 9 20 24.6 MQ H.sub.2O 10 20 0.912

TABLE-US-00006 TABLE 6 Round 6 elution regime Eluent Volume Activity Recovered (MBq) Soak Time (Hrs) Me[OH] 1 20 8.79 MQ H.sub.2O 1 20 3.01 HI 1 4 93.4 47.5 MQ H.sub.2O 2 20 721 MQ H.sub.2O 3 20 95.3 HI 2 4 12.56 22.4 MQ H.sub.2O 4 20 32.4 MQ H.sub.2O 5 20 68.9 HI 3 4 11.7 68.0 MQ H.sub.2O 6 30 18.51 MQ H.sub.2O 7 20 33.7 HI 4 4 0.728 4.6 MQ H.sub.2O 8 20 14.2 MQ H.sub.2O 9 20 4.51 HI 5 4 3.55 26.6 MQ H.sub.2O 10 20 5.98 MQ H.sub.2O 11 20 18.27

[0060] Table 7 shows the activity recovered for each generator compared to the acid soak time. It was found that the mineral acid elution itself was not as effective at carrying activity (eluting the parent radionuclide) as the water elution that followed each mineral acid elution.

TABLE-US-00007 TABLE 7 Average activity Average activity recovered after recovered after HI soak HBr soak Total Average each acid soak each acid soak time/hours time/hours acid soak length of (measured from (measured from (no. of HI (no. of HBr time/ each acid acid eluate)/ subsequent water Round elutions) elutions) hours soak/hours MBq eluate)/MBq 1 7.4 (10) 9.0 (9) 16.4 0.86 0.46 2.30 2 60.9 (5) — 60.9 12.18 1.10 5.26 3 169.2 (4) — 169.2 42.3 0.91 7.86 4 114.9 (4) — 114.9 28.73 5.48 15.01 5 93.4 (8) — 93.4 11.68 0.52 10.67 6 169.1 (5) — 169.1 33.82 24.39 158.42

Isolation and Purification of Ge-68

[0061] The methanol eluates were evaporated to near dryness and the remaining Ge-68 extracts were dissolved in an excess of dilute hydrochloric acid (0.05 M). The hydroiodic/hydrobromic eluates and the aqueous eluates were each mixed with chloroform and the chloroform phases containing .sup.68GeI.sub.4 and/or .sup.68GeBr.sub.4 were retained. The chloroform phases were evaporated to dryness and the extracts dissolved in a small quantity of methanol and then diluted with an excess of hydrochloric acid (0.05 M). The resulting hydrochloric acid solution containing Ge-68 as .sup.68GeI.sub.4 and/or .sup.68GeBr.sub.4 was loaded into a new Ge-68/Ga-68 generator column. The new generator columns containing the recycled Ge-68 were confirmed to be effective in producing the Ga-68 daughter radionuclide using the standard method of eluting with dilute hydrochloric acid (0.05 M).

[0062] Although commercial Ge-68/Ga-68 generators are typically prepared by loading the column with .sup.68GeCl.sub.4 in dilute hydrochloric acid, it was found that higher homologues such as .sup.68GeI.sub.4 and .sup.68GeBr.sub.4 behave identically to .sup.68GeCl.sub.4 as regards loading new generator columns.

EXAMPLE 2

Yield of Ge-68

[0063] The yield of Ge-68 obtained from each elution regime was assessed by measuring the radioactivity of each eluate emerging from the generator column using a CRC®-55tR Dose Calibrator (Captintec, Inc.).

[0064] The total activity recovered (% yield) as a function of the number of elutions is shown in FIGS. 2 and 3A-E. The results show that a high yield percentage (>88%) could be obtained regardless of the age of the generator (see Table 8).

[0065] Without wishing to be bound by theory, it is thought that elution with alcohol, e.g. methanol, removes Ge-68 in chelate form with laurylgallate, as well as laurylgallate itself, from the generator. It was found that the first methanol elution from each elution regime removed a significant yield of Ge-68, whereas subsequent methanol elutions were substantially diminished in activity relative to the first alcohol elution.

[0066] In contrast, it is thought that the mineral acid elution (e.g. HI and/or HBr) is complementary to the alcohol elution and primarily targets Ge-68 bonded to silica. Removal of Ge-68 from the silica matrix is thought to be crucial for high yield recovery. The method exemplified in the present application for a generator with a silica stationary phase may be applied to all oxidic substrates commonly used for radionuclide generator columns, for example, alumina (Al.sub.2O.sub.3), zirconia (ZrO.sub.2), titanium oxide (TiO.sub.2), tin oxide (SnO.sub.2), tantalum oxide (Ta.sub.2O.sub.5), vanadium oxide (V.sub.2O.sub.5) and niobium oxide (Nb.sub.2O.sub.3).

TABLE-US-00008 TABLE 8 Age of generator Original Decay corrected Total activity recovered Elution Round (days) activity (MBq) current activity (MBq) (%) 1 818 1914 206.6 96.1% 2 664 1831 446.9 −100%  3 728 952 130.6 92.7% 4 52 1580 1397 93.4% 5 62 1570 1339.6 92.7% 6 87 1610 1146.5 88.2%

[0067] All citations are hereby incorporated by reference.

[0068] The present invention has been described with regard to one or more embodiments. However, it will be apparent to persons skilled in the art that a number of variations and modifications can be made without departing from the scope of the invention as defined in the claims.

[0069] The scope of the claims should not be limited by the preferred embodiments set forth in the examples but should be given the broadest interpretation consistent with the description as a whole.