Method of radioactively labeling diagnostic and therapeutic agents containing a chelating group

• US 4,707,352 A
• Filed: 01/30/1984
• Issued: 11/17/1987
• 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: Stavrianopoulos, Jannis G.
• Primary Examiner(s): Nucker, Christine M.
• Application Number:
  US06/575,397
• Time in Patent Office: 1,387 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, 536/26-28, 536/1.1
• US Class Current: 424/1.17
• 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. A method of forming a therapeutic or diagnostic agent labeled with a radioactive metal ion, which comprises:

(A) contacting

(1) an unlabeled therapeutic or 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

(2) 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 or diagnostic agent is formed by said contacting; and

(B) separating said radiolabeled therapeutic or diagnostic agent from said ion transfer material.

2. The method of claim 1, wherein the molecularly recognizable portion, is a natural constituent of a biological system.

3. The method of claim 1, wherein the molecularly recognizable portion of said agent is proteinaceous.

4. The method of claim 1, wherein the molecularly recognizable portion of said agent comprises nucleic acid.

5. The method of claim 1, wherein the molecularly recognizable portion on said agent comprises a saccharide.

6. The method of claim 1, wherein the moleculary recognizable portion of said agent comprises a hormone.

7. The method of claim 1, wherein the moleculary recognizable portion of said agent is selected from the group consisting of antigens, antibodies, hormone receptors, viruses, viral components, bacteria, bacterial compounds, cells and cellular components.

8. The method of claim 1, wherein the chelating portion comprises a diamine having four acetic acid moieties attached to the two amino groups of said diamine.

9. The method of claim 8, wherein the amino groups are covalently attached to adjacent carbon atoms.

10. The method of claim 9, wherein said chelating portion is a derivative or analog of ethylenediaminetetraacetic acid or trans-1,2-diaminocyclohexaneacetic acid.

11. The method of claim 10, wherein said chelating portion comprises a radical having the formula ##STR2## wherein R¹ is CH₂ --COOM or a C₁ -C₄ alkyl and M is hydrogen, a cationic metal or a negative charge.

12. The method of claim 1, wherein the fraction of the binding affinity of said ion transfer material for said radioactive metal ion compared to the binding affinity of said chelating portion for said radioactive ion is less than 0.1.

13. The method of claim 12, wherein said fraction is less than 0.01.

14. The method of claim 13, wherein said fraction is less than 0.001.

15. The method of claim 1, wherein said ion transfer material is a strong-acid cation-exchange resin.

16. The method of claim 15, wherein said resin is a sulfonated copolymer of styrene and a diene crosslinking agent.

17. The method of claim 16, wherein said cross-linking agent is divinylbenzene.