Extended organic cobalt and nickel magnetic complexes

• US 20020028993A1
• Filed: 04/11/2001
• Published: 03/07/2002
• Est. Priority Date: 07/21/2000
• Status: Active Grant

• Current Assignee: Hainfeld, James F.
• Original Assignee: Hainfeld, James F.
• Inventors: Hainfeld, James F.
• Granted Patent: US 6,534,039 B2
• Time in Patent Office: Days
• US Class Current: 600/420
• CPC Class Codes: A61K 49/16 Antibodies; Immunoglobulins; Fragments thereof
• CPC Class Codes: A61K 49/1866 the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid
• CPC Class Codes: A61K 49/1875 coated or functionalised with an antibody
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent

Abstract

Disclosed is a method for in vivo imaging tissue of a individual, by performing magnetic resonance imaging utilizing an extended cobalt complex as a contrast enhancement agent. The extended cobalt complex is comprised of cobalt atoms, a carboxylate ligand, an amine ligand, and a multidentate thiol-containing organic ligand, the cobalt atoms being linked to thiol groups and counter ions. The extended cobalt complex is characterized as stable, water soluble, non-aggregating, magnetic, and from 0.5 to 10 nm in size. This method is especially useful in imaging tumor tissue, and also tissue which is regenerating from a wound. The extended cobalt complex can be specifically targeted to a particular tissue to enable selective imaging of that tissue. This is done by linking the extended cobalt complex to a binding moiety which specifically binds a molecule selectively expressed in the tissue. Also disclosed is a method for visually detecting the presence of an antigen in a sample using an antibody which specifically binds the antigen, the antibody being coupled to an extended cobalt complex. In the method, the antibody is contacted to the sample under conditions appropriate for antibody-antigen binding, and the presence of the extended cobalt complex which is bound to the antigen is detected by its characteristic color or its magnetic properties.

Claims

1. A method for in vivo imaging tissue of a individual, comprising:

a) providing an extended cobalt complex which comprises cobalt atoms, a carboxylate ligand, an amine ligand, and a multidentate thiol-containing organic ligand, the cobalt atoms being linked to thiol groups and counter ions, the extended complex being characterized as;

i) stable;

ii) water soluble;

iii) non-aggregating;

iv) magnetic; and

v) from 0.5 to 10 nm in size;

b) administering the extended cobalt complex of step a) to the individual to contact the tissue with the extended cobalt complex; and

c) performing magnetic resonance imaging on the individual to image the tissue.

2. The method of claim 1 wherein the tissue is a tumor.

3. The method of claim 1 wherein the tissue is regenerating from a wound.

4. The method of claim 1 wherein the tissue is bone, muscle, cartilage, liver, pancreas, kidney, veins, arteries, lung, heart, brain, breast, colon, lymph nodes, alimentary tract, and prostate.

5. The method of claim 1 wherein the individual is human.

6. The method of claim 1 wherein the individual is an animal.

7. A method for identifying a tumor in an individual comprising:

a) providing an extended cobalt complex which comprises cobalt atoms, a carboxylate ligand, an amine ligand, and a multidentate thiol-containing organic ligand, the cobalt atoms being linked to thiol groups and counter ions, the extended complex being characterized as;

i) stable;

ii) water soluble;

iii) non-aggregating;

iv) magnetic; and

v) from 0.5 to 10 nm in size;

b) administering the extended cobalt complex of step a) into the individual to contact the tumor with the extended cobalt complex; and

c) performing magnetic resonance imaging on the individual to identify the tumor.

8. The method of claim 7 wherein the individual is human.

9. The method of claim 7 wherein the individual is an animal.

10. The method of claim 7 wherein the extended cobalt complex is linked to a targeting molecule.

11. The method of claim 10 wherein the targeting molecule is selected from the group consisting of an antibody fragment, an antibody, a polypeptide, a nucleic acid, a carbohydrate, a lipid, a synthetic molecule.

12. The method of claim 7 wherein administering step b) is by a form of administration selected from the group consisting of intraperitoneal, intravenous, intramuscular, and oral.

14. The method of claim 13 wherein the tissue is selected from the group consisting of skeletal, secretory, digestive, muscular, reproductive, circulatory, and, immunological, neurological.

15. The method of claim 13 wherein the tissue is selected from the group consisting of liver, pancreas, kidney, veins, arteries, lung, heart, brain, breast, colon, lymph nodes, alimentary tract, and prostate.

13. A method for in vivo imaging tissue in an individual, wherein the tissue is regenerating from a wound, comprising:

a) providing an extended cobalt complex which comprises cobalt atoms, a carboxylate ligand, an amine ligand, and a multidentate thiol-containing organic ligand, the cobalt atoms being linked to thiol groups and counter ions, the extended complex being characterized as;

i) stable;

ii) water soluble;

iii) non-aggregating;

iv) magnetic; and

v) from 0.5 to 10 nm in size;

b) administering the extended cobalt complex to the individual to contact the tissue with the extended cobalt complex; and

c) performing magnetic resonance imaging on the individual to image the wounded tissue.

16. A method for in vivo imaging a tissue in an individual, wherein the tissue expresses a specific molecular marker, comprising:

a) providing an extended cobalt complex which is functionally linked to a binding moiety specific for the molecular marker, wherein the extended cobalt complex comprises cobalt atoms, a carboxylate ligand, an amine ligand, and a multidentate thiol-containing organic ligand, the cobalt atoms being linked to thiol groups and counter ions, the extended complex being characterized as;

i) stable;

ii) water soluble;

iii) non-aggregating;

iv) magnetic; and

v) from 0.5 to 10 nm in size;

b) administering the extended cobalt complex of step a) to the individual to contact the molecular marker of the tissue with the extended cobalt complex; and

c) performing magnetic resonance imaging on the individual to image the tissue which expresses the molecular marker.

17. A method for visually detecting the presence of an antigen in a sample, comprising:

a) providing antibody which specifically binds the antigen, the antibody having been coupled to an extended cobalt complex which has a characteristic color;

b) contacting the antibody of step a) to the sample under conditions appropriate for antibody-antigen binding; and

c) visually detecting the presence of the extended cobalt complex in the sample via detection of the characteristic color of the extended cobalt complex, with the presence of the extended cobalt complex being an indication of the presence of the antibody and thus an indication of the presence of the antigen in the sample.

18. A method for detecting the presence of an antigen in a sample, comprising:

a) providing antibody which specifically binds the antigen, the antibody having been coupled to an extended cobalt complex which has a characteristic color;

b) contacting the antibody of step a) to the sample under conditions appropriate for antibody-antigen binding; and

c) detecting the presence of the extended cobalt complex in the sample via detection of the magnetic properties of the extended cobalt complex, with the presence of the extended cobalt complex being an indication of the presence of the antibody and thus an indication of the presence of the antigen in the sample.