Imaging brown adipose tissue with curcumin derivatives

• US 9,757,477 B2
• Filed: 09/04/2014
• Issued: 09/12/2017
• Est. Priority Date: 09/06/2013
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Ran, Chongzhao, Moore, Anna, Brownell, Anna-Liisa
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): Samala, Jagadishwar
• Application Number:
  US14/916,779
• Publication Number:
  US 20160193363A1
• Time in Patent Office: 1,104 Days
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0017 Fluorescence in vivo
• CPC Class Codes: A61K 49/06 Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
• CPC Class Codes: A61K 49/22 Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Methods and compositions for imaging Brown adipose tissue (BAT) in living mammals, e.g., humans.

Claims

1. A method of imaging brown adipose tissue (BAT) in a mammal, the method comprising:

administering to the mammal a BAT imaging agent of Formula I;

3. The method of claim 1, wherein detecting the imaging agent comprises detecting fluorescence emission from the imaging agent;

detecting gamma rays;

detecting nuclear magnetic resonance (NMR);

or detecting ultrasonic emissions.

4. The method of claim 1, wherein the BAT imaging agent is selected from the group consisting of CRANAD-2, CRANAD-3, CRANAD-29, and CRANAD-43.

5. The method of claim 1, wherein detecting the imaging agent comprises:

setting a region of interest (ROI); and

obtaining an image of the region of interest in the mammal.

6. The method of claim 5, further comprising processing the image to provide a measure of BAT levels or activity in the mammal.

8. The method of claim 5, wherein the ROI covers one or more of the cervical, supraclavicular, and superior mediastinal areas of the mammal.

9. The method of claim 1, comprising:

obtaining an image by detecting fluorescence emission from the imaging agent, or detecting ultrasonic emissions; and

processing the image to provide information regarding BAT levels or activity in the mammal.

10. The method of claim 9, comprising:

scanning the ROI with an infrared camera to obtain an infrared thermographic image of the region of interest in the mammal;

processing the image to provide a measure of temperature information;

wherein the temperature information provides information regarding BAT levels or activity in the mammal.

11. The method of claim 1, wherein the imaging agent comprises a positron-emitting radionuclide, and the method comprises:

obtaining an image by detecting gamma radiation from the BAT imaging agent; and

processing the image to provide information regarding BAT levels or activity in the mammal.

12. The method of claim 1, wherein the imaging agent comprises ¹³C, ¹⁷O, or ¹⁹F atom, and the method comprises:

obtaining an image by detecting BAT using an imaging modality suitable for detecting the spin of those labeled agents; and

processing the image to provide information regarding BAT levels or activity in the mammal.

14. The method of claim 12, wherein the predetermined value is a measure of BAT levels or activity in the ROI of the same subject before or after administration of a test compound, wherein the comparison indicates an effect of the test compound on BAT levels or activity.

2. A method of detecting brown adipose tissue (BAT) levels or activity in a mammal, the method comprising:

administering to the mammal a BAT imaging agent of Formula I;

7. The method of claim 2, comprising one or both of:

administering CRANAD-2 to the mammal, and processing the image to provide a measure of BAT activity, and/or

administering CRANAD-29 to the mammal, and processing the image to provide a measure of BAT levels.

13. The method claim 2, further comprising comparing the measure of BAT levels or activity to a predetermined value, the predetermined value being a measure of BAT levels or activity in either the same subject, or a measure that represents BAT levels or activity in one or more control subjects.

19. The method of claim 2, further comprising selecting, rejecting, or stratifying the subject for participation in a clinical trial based on BAT levels or activity in the subject.

20. The method of claim 2, further comprising comparing the measure of BAT levels or activity in the mammal to a subsequent measure of BAT levels or activity obtained after administration of a test compound, to detect an increase, decrease, or no change in BAT levels or activity in the mammal;

thereby determining the effect of the test compound on BAT levels or activity in the mammal.

15. A method of detecting an effect of a test compound on brown adipose tissue (BAT) levels or activity in a mammal, the method comprising:

administering a test compound to the mammal;

administering to the mammal a BAT imaging agent of Formula I;

16. The method of claim 15, further comprising selecting a test compound that increases BAT levels or activity in the mammal as a candidate compound for the treatment of obesity or a metabolic disorder.

17. The method of claim 15, wherein detecting the imaging agent in the mammal comprises setting a region of interest (ROI);

and obtaining an image of the region of interest in the mammal.

18. The method of claim 17, wherein the ROI includes an area comprising white adipose tissue (WAT) in the subject, and an increase in BAT levels or activity in the ROI indicates that the test compound induces or enhances browning of white fat.