Large stoke shift dye used for optical imaging

• US 20080206886A1
• Filed: 02/28/2007
• Published: 08/28/2008
• Est. Priority Date: 02/28/2007
• Status: Active Grant

• Current Assignee: Bruker Biospin Corporation (Bruker Corporation)
• Original Assignee: CareStream Health Incorporated
• Inventors: Schmitthenner, Hans F., Harder, John W., Stegman, David A., Wang, Ruizheng, Harrison, William J.
• Granted Patent: US 8,017,104 B2
• Time in Patent Office: Days
• US Class Current: 436/172
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 49/0058 Antibodies
• CPC Class Codes: C07D 209/14 Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 277/64 with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C09B 23/0016 the substituent being a halogen atom
• CPC Class Codes: C09B 23/0033 the substituent being bound through a sulfur atom
• CPC Class Codes: C09B 23/0041 the substituent being bound through a nitrogen 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 23/086 more than five >CH- groups
• CPC Class Codes: G01N 33/533 with fluorescent label
• CPC Class Codes: Y10S 430/145 Infrared

Abstract

The present invention relates to a diagnostic contrast agent comprising a water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 and represented by five general formulae. The present invention also relates to a method for making a dye-conjugate utilizing the novel dye and a method of identifying a biological compound using the novel dye conjugate.

Claims

1. A diagnostic contrast agent comprising a water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 and represented by the following five general formulae:

2. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 and represented by Formula I-V has a carboxyethylpiperazine (enamine) bridging group.

3. The diagnostic contrast agent of claim 1 wherein Ra and Rb are methyl.

4. The diagnostic contrast agent of claim 1 wherein at least one of R1, R2, R3, R4 independently represents COOH.

5. The diagnostic contrast agent of claim 1 wherein said Stoke shift is from 70 to 140.

6. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye has a max excitation wavelength between 500 and 900 nm.

7. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye has a max excitation wavelength between 500 and 900 nm and has a maximum emission wavelength which is at least 70 nm greater in wavelength than the max excitation wavelength.

8. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is:

9. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is at least one member of the group represented by:

10. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is attached to biocompatible particles, biocompatible beads, microbeads or nanoparticles.

11. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is attached to peptides, proteins, antibodies or oligonucleotides.

12. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is attached to at least one drug.

13. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is attached to at least one cell.

14. The diagnostic contrast agent of claim 1 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 is attached to at least one non-biological materials selected from the group consisting of soluble polymers, polymeric particles, glass and polymeric surfaces, and monomers.

15. A method of making diagnostic contrast agent conjugate comprising:

providing a water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 and represented by the following five general formulae;

16. The method of claim 15 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye is attached to peptides, proteins, antibodies or oligonucleotides.

17. A method of identifying a biological compound comprising:

providing at least one diagnostic contrast agent comprising at least one water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 and represented by the following five general formulae;

18. The method of claim 17 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye has a max excitation wavelength between 500 and 900 nm.

19. The method of claim 17 wherein said water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye has a max excitation wavelength between 500 and 900 nm and has a maximum emission wavelength which is at least 70 nm greater in wavelength than the max excitation wavelength.