TARGETED, NIR IMAGING AGENTS FOR THERAPY EFFICACY MONITORING, DEEP TISSUE DISEASE DEMARCATION AND DEEP TISSUE IMAGING

• US 20100278739A1
• Filed: 07/13/2010
• Published: 11/04/2010
• Est. Priority Date: 01/03/2005
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Wyatt, Shelby K., Manning, H. Charles, Bornhop, Darryl J., Bai, Mingfeng
• Granted Patent: US 8,372,868 B2
• Time in Patent Office: Days
• US Class Current: 424/9.1
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: G01N 33/582 with fluorescent label

Abstract

Compounds and methods related to NIR molecular imaging, in-vitro and in-vivo functional imaging, therapy/efficacy monitoring, and cancer and metastatic activity imaging. Compounds and methods demonstrated pertain to the field of peripheral benzodiazepine receptor imaging, metabolic imaging, cellular respiration imaging, cellular proliferation imaging as targeted agents that incorporate signaling agents.

Claims

1. A method of imaging a molecular event in a sample, comprising:

(a) administering to said sample a probe having an affinity for a target, the probe comprising at least one of a ligand/signaling agent combination, or conjugable form of a ligand/signaling agent combination; and

(b) detecting a signal from said probe.

2. The method of claim 1, wherein said sample is at least one of cells, tissue, cellular tissue, serum, cell extract, bodily fluids.

3. The method of claim 2, wherein the bodily fluids are breast milk, sputum, vaginal fluids, urine.

4. The method of claim 1, wherein the administering step is in vivo or in vitro.

5. The method of claim 1, wherein said molecular event is at least one of peripheral benzodiazepine receptor expression, cell proliferation, glucose uptake, epidermal growth factor receptor expression, microglial activation, apoptosis, matrix metalloproteinase activation.

6. The method of claim 1, wherein said signaling agent is a near infrared signaling agent.

7. The method of claim 1, wherein said detecting step comprises near infrared detection.

9. The method of claim 1, further comprising the step of:

analyzing said signal to diagnose a disease state.

10. The method of claim 7, wherein the disease state is cancer, neurodegenerative disease, cancer, multiple sclerosis, epilepsy.

11. The method of claim 9, wherein the disease state is brain cancer or breast cancer.

12. The method of claim 1, wherein the signaling agent is a cyanine dye.

13. The method of claim 1, wherein the signaling agent is a compound of the following formula:

14. The method of claim 1, wherein said probe comprises a peripheral benzodiazepine affinity ligand or a conjugable form thereof.

15. The method of claim 14, wherein the peripheral benzodiazepine affinity ligand or conjugable form thereof is at least one of the following compounds:

16. The method of claim 14, wherein the peripheral benzodiazepine affinity ligand is a compound of the following formula:

17. The method of claim 14, wherein the peripheral benzodiazepine affinity ligand is a compound of the following formula:

18. The method of claim 14, wherein the peripheral benzodiazepine affinity ligand is a compound of the following formula:

19. The method of claim 14, wherein the peripheral benzodiazepine affinity ligand is a compound of the following formula:

20. The method of claim 1, wherein the signaling agent is a compound of the formula:

8. The method of claim 8, wherein the near infrared detection included near infrared imaging.

21-22. -22. (canceled)

23. A compound of the following formula:

24. The compound of claim 23, wherein the signaling moiety is a dye.

25. A compound of the following formula:

26. The compound of claim 25, wherein the signaling moiety is a dye.

27. A compound of the following formula:

28. The compound of claim 27, wherein the signaling moiety is a dye.

29-47. -47. (canceled)

48. A method of quantifying the progression of a disease state in a subject, comprising:

(a) administering to a first sample of the subject a conjugate, the conjugate comprising a peripheral benzodiazepine affinity ligand or conjugable form thereof or a conjugable deoxythymidine compound and a signaling agent;

(b) detecting a signal from said conjugate;

(c) after a period of time from step (b), administering to a second sample of the subject a conjugate, the conjugate comprising a peripheral benzodiazepine affinity ligand or conjugable form thereof or a conjugable deoxythymidine compound and a signaling agent;

(d) detecting a second signal; and

(e) comparing the first signal with the second signal to determine the progress of a disease state.

49. The method of claim 48, wherein said sample is at least one of cells, tissue, cellular tissue, serum, cell extract, bodily fluid.

50. The method of claim 49, wherein the bodily fluid is selected from breast milk, urine, vaginal fluids, sputum.

51. The method of claim 48, wherein the conjugable compound is of the following formula:

52. The method of claim 48, wherein the disease state is cancer, neurodegenerative disease, coronary disease.

53. The method of claim 48, wherein the disease state is breast cancer, non-Hodgkin'"'"'s lymphoma, or colon cancer.

54. The method of claim 48, wherein the conjugable compound of the following formula:

55. The method of claim 48, wherein the period of time between step (b) and the administering to a second sample step, includes a treatment step for said disease state.

56-70. -70. (canceled)