Therapeutic and diagnostic processes using isotope transfer to chelator-target recognition molecule conjugate

• US 4,767,609 A
• Filed: 01/23/1987
• Issued: 08/30/1988
• Est. Priority Date: 01/30/1984
• Status: Expired due to Term

• Current Assignee: Enzo Therapeutics Incorporated (Enzo Biochem Incorporated)
• Original Assignee: Enzo Biochem Incorporated
• Inventors: Stavrianpoulos, Jannis G.
• Primary Examiner(s): Nucker, Christine M.
• Application Number:
  US07/006,818
• Time in Patent Office: 585 Days
• Field of Search: 424/1.1, 424/9, 424/85, 424/88, 424/89, 424/92, 530/350, 530/402, 530/403, 530/405, 530/406, 536/1.1, 536/26-28, 422/61
• US Class Current: 424/1.45
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: A61K 51/12 characterised by a special physical form, e.g. emulsion, microcapsules, liposomes , characterized by a special physical form, e.g. emulsions, dispersions, microcapsules liposomes A61K51/1234
• CPC Class Codes: G01N 33/534 with radioactive label
• CPC Class Codes: G01N 33/60 involving radioactive labelled substances
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 436/804 Radioisotope, e.g. radioimmunoassay
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

A method of forming a therapeutic or diagnostic agent labeled with a radioactive metal ion, which comprises: contacting an unlabeled therapeutic or diagnostic agent, consisting of a substantially non-metal chelating portion and a chelating portion capable of chelating with the radioactive metal ion, with an ion transfer material having the radioactive metal ion bound thereto and having a binding affinity for the radioactive metal less than the binding affinity of the chelating portion for the radioactive metal ion, wherein prior to contacting the chelating portion is unchelated or is chelated with a second metal having a binding affinity with the chelating portion less than the binding affinity of the radioactive metal ion, whereby a radiolabeled therapeutic or diagnostic agent is formed by the contacting, and separating the radiolabeled therapeutic or diagnostic agent from the ion transfer material, is disclosed along with various components and kits useful in practicing this method and several variations thereof.

Claims

1. An in vivo diagnostic method, which comprises:

(1) forming a diagnostic agent labeled with a radioactive metal ion by contacting

(i) an unlabeled diagnostic agent comprising

(a) a molecularly recognizable portion attached to

(b) a chelating portion capable of substantially chelating with said radioactive metal ion, wherein said chelating portion is not a part of said molecularly recognizable portion, with

(ii) an ion transfer material having said radioactive metal ion bound thereto and having a binding affinity for said radioactive metal ion less than the binding affinity of said chelating portion for said radioactive metal ion.

wherein, prior to said contacting, said chelating portion is unchelated or is chelated with a second metal having a binding affinity with said chelating portion less than the binding affinity of said radioactive metal ion, whereby a radiolabeled diagnostic agent is formed by said contacting; and

(2) separtating, if necessary, said ion transfer material from said radiolabeled diagnostic agent;

(3) administering said agent to a human or animal; and

(4) detecting radiation emitted by said radioactive metal ion.

2. The method of claim 1, wherein said radiation is gamma radiation.

3. The method of claim 1, wherein said agent selectively localizes in a target region of said human or animal by interaction of a molecularly recognizable portion of said agent with a complementary substance in said target region.

4. The method of claim 3, wherein said complementary substance is a polynucleotide sequence, antigen, antibody, sugar, hormone, hormone receptor, enzyme, enzyme substrate or enzyme cofactor.

5. The method of claim 3, wherein the molecularly recognizable portion of said agent is an antibody.

6. The method of claim 1, wherein the chelating portion of said agent comprises 1,2-diaminocyclohexaneacetic acid or an analogue thereof.

7. A therapeutic process which comprises:

(1) forming a therapeutic agent labeled with a radioactive metal ion by contacting

(i) an unlabeled therapeutic agent comprising

(a) a molecularly recognizable portion attached to

(b) a chelating portion capable of substantially chelating with said radioactive metal ion, wherein said chelating portion is not a part of said molecularly recognizable portion, with

(ii) an ion transfer material having said radioactive metal ion bound thereto and having a binding affinity for said radioactive metal ion less than the binding affinity of said chelating portion for said radioactive metal ion.

wherein, prior to said contacting, said chelating portion is unchelated or is chelated with a second metal having a binding affinity with said chelating portion less than the binding affinity of said radioactive metal ion, whereby a radiolabeled therapeutic agent is formed by said contacting; and

(2) separating, if necessary, said ion transfer material radiolabeled therapeutic agent;

(3) administering said agent to a human or animal wherein said agent selectively localizes in a target region of said human or animal, therety concentrating radiation from said radioactive metal ion in said target region.

8. The process of claim 7, wherein said radiation is beta radiation.

9. The method of claim 7, wherein said agent localizes in a target region of said human or animal by interaction of a molecularly recognizable portion of said agent with a complementary substance in said target region.

10. The method of claim 9, wherein said complementary substance is a polynucleotide sequence, antigen, antibody, sugar, hormone, hormone receptor, enzyme, enzyme substrate or enzyme cofactor.

11. The method of claim 9, wherein the molecularly recognizable portion of said agent is an antibody.

12. The method of claim 7, wherein the chelating portion of said agent comprises 1,2-diaminocyclohexaneacetic acid or an analogue thereof.

13. A kit suitable for forming an in vivo therapeutic or diagnostic agent labeled with a radioactive metal ion, which comprises:

(A) carrier means compartmentalized to receive in close confinement therein one or more containers;

(B) a first container confined within said carrier and containing a therapeutic or diagnostic agent consisting of

(1) a substantially non-metal chelating portion attached to

(2) a chelating portion capable of chelating with a radioactive metal ion; and

(C) a second container confined within said carrier and containing an ion transfer material capable of binding said radioactive metal ion bound thereto wherein the binding affinity of said ion transfer material for said radioactive metal ion is less than the binding affinity of said chelating portion for said radioactive metal ion.

14. The kit of claim 13, wherein said radioactive metal ion is bound to said ion transfer material in said second container.

15. The kit of claim 13, wherein said second container (C) is fitted with fluid inlet and outlet means and with confining means which prevent the exit of said ion transfer material from said second container (C).

16. The kit of claim 13, wherein said second container (C) is columnar with said inlet and outlet means being at opposite ends and said confining means confine said ion transfer material between said inlet means and said outlet means wherein fluid inserted into said inlet means intimately contacts said ion transfer material while passing through said container means prior to exiting through said outlet means.

17. The kit of claim 13, wherein said ion transfer material is a strong-acid cation-exchange resin.

18. The kit of claim 17, wherein said resin is a sulfonated copolymer of styrene and a diene crosslinking agent.

19. The kit of claim 18, wherein said crosslinking agent is divinylbenzene.

20. The kit of claim 19, wherein said resin is porous.

21. The kit of claim 13, wherein the substantially non-metal chelating portion of said agent comprises an antibody, hormone, enzyme, enzyme substrate, enzyme cofactor, lipid, saccharide, polynucleotide sequence, virus, virus fragment, cell, or cell fragment.

22. The kit of claim 21, wherein said substantially non-metal chelating portion comprises an antibody.

23. The kit of claim 21, wherein said substantailly non-metal chelating portion comprises a polynucleotide sequence.

24. The kit of claim 13, wherein the chelating portion of said agent comprises 1,2-diaminocyclohexaneacetic acid or an analogue thereof.

25. The kit of claim 13, wherein said kit further comprises a third container confined within said carrier means and containing an eluent capable of eluting said agent from said ion transfer material.

26. The kit of claim 13, wherein said kit further comprises administering means, whereby said agent can be administered to a human or animal by use of said administering means.

27. The kit of claim 26, wherein said administering means is a disposable syringe adapted for accepting said agent as said agent exits from said second container (C).