Process and apparatus for separation of technetium-99M from molybdate

1. A method of separating technetium-99m (Tc-99m) from one or more contaminants comprising:

obtaining a target solution comprising technetium-99m (Tc-99m) and one or more contaminants;

loading the target solution on a solid support consisting of a polyalkyl glycol-based cross-linked polyether polymer under conditions favouring interaction of the technetium-99m (Tc-99m) with the solid support;

washing the solid support under conditions favouring interaction of the technetium-99m (Tc-99m) with the solid support; and

eluting the technetium-99m (Tc-99m) from the solid support with an elution solution under conditions promoting release of the technetium-99m (Tc-99m) from the solid support.

2. A method as defined in claim 1 , wherein the solid support comprises a cross-linked polyether which is obtained by polymerizing a monomer of the general formula:

wherein A is a polyalkyl glycol and B and C are independently electron-withdrawing groups.

3. A method as defined in claim 2 , wherein the polyalkyl glycol comprises polyethylene glycol (PEG), polypropylene glycol (PPG), polytetrahydrofuran (poly(THF)), or a combination thereof, and wherein the electron-withdrawing groups B and C independently comprise cyano, ester, amide, formyl, halogen, nitro, sulfoxide, or ketone.

4. A method as defined in claim 1 , wherein the solid support comprises a cross-linked polyether which is obtained by copolymerization of at least one monomer comprising (a) a one-ended polymerizable vinyl or allyl ketone, ester, ether or mixtures thereof with at least one cross-linker having at least two polymerizable terminal end groups, with the exception of epoxy and oxetane end groups, or (b) divinyl benzene; wherein the solid support is obtained by copolymerizing at least one monomer derivative of an acrylic, methacrylic, maleic and/or itaconic acid with (a) at least one cross-linker having at least two polymerizable terminal end groups, with the exception of epoxy and oxetane end groups, or (b) divinyl benzene to produce a cross-linked polyester; and wherein the cross-linked polyester is reduced to give a cross-linked polyol resin, and the cross-linked polyol resin is reacted with a cyclic ether or a cyclic amine to yield the cross-linked polyether solid support.

5. A method as defined in claim 1 , wherein the solid support comprises a polyethylene glycol-based cross-linked polyether polymer having the general formula (1), (2), (3), (4), (5), (6) (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (26), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (40), (41), (42), (43), (44), (45), (46) or (47) set forth below, wherein R′ and R″ can independently be alkyl, aryl or hydrogen, wherein n is an integer between 1 and 1000, and wherein m is an integer between 1 and 1000:

6. A method as defined in claim 1 , wherein the solid support comprises a polyalkyl glycol-based cross-linked polyether polymer having the general formula (48) below

wherein Z is an alkyl group and W is: (a) any one of the structures specified for X in structures (22), (23), (24), (25), (26), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (40), or (41)

X ═CH 3   22—

X═NO 2   23—

X═CH 2 OH  24—

X═CH 2 SH  25—

X═CH 2 NR′R″  26—

X═CH 2 PR′R″  27—

X=alkane  28—

X=alkene  29—

X=alkane  30—

X=arene  31—

X═OR′  32—

X═C(O)OR′  33—

X═COOH  34—

X═C(O)NR′R″  35—

X═C(S)NR′R″  36—

X═Cl  37—

X═F  38—

X═Br  39—

X═I  40—

X═SO 3   41—

(b) —CH 2 —NH—R, where R is any one of the structures specified for R in structures (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), or (21)

(c) —CH 2 —Y, where Y is any one of the structures specified for Y in structures (42), (43), (44), (45), (46) or (47)

or

(d) one of the following structures (52), (53), (54), (55) or (56)

7. A method as defined in claim 6 , wherein Z is —CH 2 CH 2 —, —CH(CH 3 )CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or a mixture thereof.

8. A method as defined in claim 1 , wherein the solid support comprising a polyalkyl glycol-based cross-linked polyether polymer has been modified by one or more of: (1) inactivating primary amine groups of the polyalkyl glycol-based cross-linked polyether polymer by the formation of amides, carbamates, ureas, sulfonamides, phosphinamides, phosphoramides, sulfenamides, or imines; (2) converting primary amine groups of the polyalkyl glycol-based cross-linked polyether polymer to other functional groups including secondary amine, tertiary amine, nitro, hydroxy, hydrocarbon, ether, halide, nitrile, ester, or acid; (3) preparing the polyalkyl glycol-based cross-linked polyether polymer in a manner that renders the polyalkyl glycol-based cross-linked polyether polymer devoid of amino groups; or (4) adding polyalkyl glycol groups of various lengths to primary amine groups of the polyalkyl glycol-based cross-linked polyether polymer.

9. A method as defined in claim 1 , wherein the solid support does not comprise polystyrene.

10. A method as defined in claim 1 , wherein the Tc-99m is obtained by neutron capture of Mo-98, by irradiation of highly enriched uranium (HEU) or low enriched uranium (LEU), by a proton-induced process using a linear accelerator to bombard a natural or enriched molybdenum target comprising Mo-100, by using a medical cyclotron to bombard a natural or enriched molybdenum target comprising Mo-100, by a deuteron-induced process using a linear accelerator or a cyclotron to bombard a natural or enriched molybdenum target comprising Mo-100, or by accelerator-based photon or electron-photon induced production of Mo-99.

11. A method as defined in claim 1 , wherein the one or more contaminants comprise molybdenum-98 (Mo-98), molybdenum-99 (Mo-99), or molybdenum-100 (Mo-100).

12. A method as defined in claim 11 , wherein the conditions favouring interaction of the technetium-99m (Tc-99m) with the solid support comprise basic conditions, wherein the basic conditions comprise a pH of about 8 or higher, or wherein the conditions promoting release of the technetium-99m (Tc-99m) from the solid support comprise neutral or acidic conditions, wherein the neutral or acidic conditions comprise a pH of about 7 or lower.

13. A method as defined in claim 1 , wherein the conditions favouring interaction of the technetium-99m (Tc-99m) with the solid support comprise the presence of a sufficient amount of an ammonium or alkali metal cation and one or more of the following anions: hydroxide, fluoride, carbonate, silicate, sulphate, phosphate, dihydrogen phosphate, hydrogen phosphate, formate, succinate, tartrate, citrate, chromate, molybdate, tungstate, orthovanadate, thiocyanate, thiosulfate, fluorosilicate, orthosilicate, hydroxyethane-1,1-diphosphonate, or vinylidene-1,1-diphosphonate, wherein the concentration of the anion is about 0.05 molar or higher, and wherein the conditions promoting release of the technetium-99m (Tc-99m) from the solid support comprise a reduction in the concentration of the anion.

14. A method as defined in claim 1 , wherein the solution eluted from the solid support is passed through a strong cation exchange resin.

15. A method as defined in claim 14 , wherein the solution eluted from the solid support is passed through an alumina cartridge after the solution eluted from the solid support has been passed through the strong cation exchange resin, so that the technetium-99m (Tc-99m) binds to the alumina cartridge and is subsequently eluted with a saline solution.

16. A method of preparing a solid support useful for the separation of technetium-99m (Tc-99m) from one or more contaminants including molybdenum (Mo), the method comprising reacting a solid support having the structure (1)

wherein n is an integer between 1 and 1000, with:

(a) acetic anhydride and N,N-diisopropylethylamine in methylene chloride to produce a solid support having the general chemical structure (2)

(b) methanesulfonyl chloride and N,N-diisopropylethylamine in methylene chloride to produce a solid support having the general chemical structure (3)

(c) poly(ethylene glycol) methyl ether tosylate and potassium carbonate in acetonitrile to produce a solid support having the general chemical structure (4) wherein m is an integer between 1 and 1000

or (d) di-tert-butyl dicarbonate and N,N-diisopropylethylamine in methanol to produce a solid support having the general chemical structure (5)

or, the method comprising reacting a solid support having the general structure below wherein Z is an alkyl group

with:

(a) acetic anhydride and N,N-diisopropylethylamine in methylene chloride to produce a solid support having the general chemical structure (52)

(b) methanesulfonyl chloride and N,N-diisopropylethylamine in methylene chloride to produce a solid support having the general chemical structure (53)

(c) poly(ethylene glycol) methyl ether tosylate and potassium carbonate in acetonitrile to produce a solid support having the general chemical structure (54) wherein m is an integer between 1 and 1000

or (d) di-tert-butyl dicarbonate and N,N-diisopropylethylamine in methanol to produce a solid support having the general chemical structure (55)

17. A method as defined in claim 16 , wherein Z is —CH 2 CH 2 —, —CH(CH 3 )CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or a mixture thereof.

18. A method for separating Technetium-99m (Tc-99m) from one or more contaminants including molybdenum (Mo), the method comprising using a solid support consisting of the general chemical structure (2), (3), (4), or (5) below, wherein n is an integer between 1 and 1000 and wherein in is an integer between 1 and 1000:

or having the general chemical structure (52), (53), (54), or (55) below, wherein m is an integer between 1 and 1000, and wherein Z comprises an alkyl group