RECEPTOR-AVID EXOGENOUS OPTICAL CONTRAST AND THERAPEUTIC AGENTS

• US 20100022449A1
• Filed: 05/21/2009
• Published: 01/28/2010
• Est. Priority Date: 03/09/2006
• Status: Abandoned Application

• Current Assignee: Medibeacon Development LLC
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Bugaj, Joseph E., Rajagopalan, Raghavan, Dorshow, Richard B., Achilefu, Samuel I.
• Application Number:
  US12/470,310
• Publication Number:
  US 20100022449A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C09B 23/0016 the substituent being a halogen atom
• CPC Class Codes: C09B 23/0025 the substituent being bound through an oxygen atom
• CPC Class Codes: C09B 23/0066 the polymethine chain being part of a carbocyclic ring,(e.g. benzene, naphtalene, cyclohexene, cyclobutenene-quadratic acid)
• CPC Class Codes: C09B 23/0075 the polymethine chain being part of an heterocyclic ring
• CPC Class Codes: C09B 23/086 more than five >CH- groups

Abstract

Cyanine and indocyanine dye compounds and bioconjugates are disclosed. The present invention includes several cyanine and indocyanine dyes, including bioconjugates of the same, with a variety of bis- and tetrakis (carboxylic acid) homologues. The compounds of the invention may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of compounds of the invention allows favorable delivery to tumor cells as compared to larger molecular weight imaging agents. Further, use of a biocompatible organic solvent such as dimethylsulfoxide may be said to assist in maintaining the fluorescence of compounds of the invention. The compounds and bioconjugates herein disclosed are useful in a variety of medical applications including, but not limited to, diagnostic imaging and therapy, endoscopic applications for the detection of tumors and other abnormalities, localized therapy, photoacoustic tumor imaging, detection and therapy, and sonofluorescence tumor imaging, detection and therapy.

Claims

1. A method of using the compound of the following formula in a diagnostic procedure comprising administering to an individual the compound

each A is independently —

CH₂ or —

CH₂OCH₂;

R is —

CONH-peptide;

R′

is R or —

COOH; and

each n is independently 1-6, and

detecting the compound to perform the diagnostic procedure.

2. The method of claim 1 wherein R′

in the compound is R.

3. The method of claim 1 wherein R′

in the compound is —

COOH.

4. The method of claim 1 wherein the peptide in the compound is octreotide.

5. The method of claim 1 wherein the peptide in the compound is octreotate.

6. The method of claim 1 wherein the peptide in the compound is bombesin.

7. The method of claim 1 wherein the peptide in the compound is cholecystokinin.

8. The method of claim 1 wherein the peptide in the compound is neurotensin.

9. The method of claim 1 wherein n in the compound is 1.

10. The method of claim 1 wherein n in the compound is 4.

11. The method of claim 1 wherein n in the compound is 6.

12. The method of claim 1 wherein each A in the compound is —

CH₂, and each n in the compound is 1.

13. The method of claim 12 wherein R′

in the compound is —

COOH.

14. The method of claim 13 wherein the peptide in the compound is octreotate.

15. The method of claim 13 wherein the peptide in the compound is octreotide.

16. The method of claim 12 wherein the peptide in the compound is octreotate.

17. The method of claim 13 wherein the peptide in the compound is bombesin.

18. The method of claim 13 wherein the peptide in the compound is cholecystokinin.

19. The method of claim 13 wherein the peptide in the compound is neurotensin.

20. The method of claim 12 wherein R′

in the compound is R, and peptide in the compound is octreotate.