Description of Invention:
Available for licensing and commercial development are two novel classes of compounds useful as radioligands for in vivo imaging of beta-amyloid peptides and plaques in humans.
Beta-amyloid peptide deposition in the brain is a pathological feature of Alzheimer’s disease (AD). Early detection of beta-amyloid load in patients with suspected AD is vital to initiating early treatment, which can improve cognitive function and quality of life for many patients.
The invention describes novel derivatives of imidazopyridinylbenzeneamine (IMPY) and benzothizolylbenzeneamine (BTA), which demonstrate high in vitro binding affinity to human beta-amyloid. The difference between existing IMPY compounds and the novel derivatives is the substitution of an aryl halide with an aryl thioether group and replacement of a sulfur group of the pyridine ring with a nitrogen group. The new classes of compounds have the potential of providing improved amyloid imaging agents for Positron Emission Tomography (PET) with higher specificity for amyloid, low background noise, better entry into the brain and improved labeling efficiency.
In addition to the novel compounds, the invention also includes: 1) a new method of synthesizing the IMPY derivatives, using palladium as a catalyst, 2) methods of imaging beta-amyloid deposits in the brain by in vivo PET, magnetic resonance imaging (MRI) and other imaging methods involving the use of these compounds, and 3) and methods of labeling these compounds with radiotracers ([11-C] and [18-F]).
Inventors:
Lisheng Cai (NIMH) Victor Pike (NIMH) Robert Innis (NIMH)
Patent Status:
DHHS Reference No. E-156-2006/0 --
U.S. Provisional Application No. 60/793,807 filed 21 Apr 2006
PCT Application No. PCT/US2007/066939 filed 19 Apr 2007, which published as WO 2007/124345 on 27 Mar 2008
U.S. Patent Application No. 12/293,340 filed 17 Sep 2008
Relevant Publication:
L Nichols, VW Pike, L Cai, RB Innis. Imaging and in vivo quantitation of beta-amyloid: an exemplary biomarker for Alzheimer's disease? Biol Psychiatry. 2006 May 15;59(10):940-947.
[PubMed abs]
H Toyama et al. PET imaging of brain with the beta-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2005 May;32(5):593-600.
[PubMed abs]
L Cai et al. Synthesis and evaluation of two 18F-labeled 6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine derivatives as prospective radioligands for beta-amyloid in Alzheimer's disease. J Med Chem. 2004 Apr 22;47(9):2208-2218. [PubMed abs]
Licensing Status: Available for non-exclusive or exclusive licensing.
Collaborative Research Opportunity:
The NIMH Molecular Imaging Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Beta-Amyloid PET Imaging Agents. Please contact Suzanne Winfield at winfiels@mail.nih.gov for more information.
Portfolios: Internal Medicine Devices/Instrumentation
For Additional Information Please Contact: Michael Shmilovich J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5019
Email: shmilovm@mail.nih.gov
Fax: (301) 402-0220
