Targeted, NIR imaging agents for therapy efficacy monitoring, deep tissue disease demarcation and deep tissue imaging

• US 8,372,868 B2
• Filed: 07/13/2010
• Issued: 02/12/2013
• Est. Priority Date: 01/03/2005
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Bornhop, Darryl J., Manning, H. Charles, Bai, Mingfeng, Wyatt, Shelby K.
• Primary Examiner(s): NORTHINGTON DAVIS, ZINNA
• Application Number:
  US12/835,448
• Publication Number:
  US 20100278739A1
• Time in Patent Office: 945 Days
• Field of Search: None
• US Class Current: 514/352
• 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 compound of the following formula:

2. The compound of claim 1, wherein the signaling moiety is a dye.

3. A compound of claim 2, of the following formula:

11. The method of claim 1, wherein the near infrared detection includes near infrared imaging.

4. 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 said ligand/signaling agent combination; and

(b) detecting a signal from said probe;

wherein said ligand is a compound of the following formula;

5. The method of claim 4, wherein said sample is at least one of cells, tissue, cellular tissue, serum, cell extract, bodily fluids.

6. The method of claim 5, wherein the bodily fluids are breast milk, sputum, vaginal fluids, urine.

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

8. The method of claim 4, 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.

9. The method of claim 4, wherein said signaling agent is a near infrared signaling agent.

10. The method of claim 4, wherein said detecting step comprises near infrared detection.

12. The method of claim 4, further comprising the step of:

analyzing said signal to diagnose a disease state.

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

14. The method of claim 12, wherein the disease state is brain cancer or breast cancer.

15. The method of claim 4, wherein the signaling agent is a cyanine dye.