Two novel classes of compounds useful as radioligands for in vivo imaging of beta-amyloid peptides and plaques in humans

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. (Diagram of radioligand structure may be viewed at http://www.ott.nih.gov/db/abstxt.asp?refno=1359.) 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]). Publications: 1. 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. E-pub 2006 Feb 17, doi:10.1016/j.biopsych.2005.12.004. 2. 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. E-pub 2005 Mar 25, doi:10.1007/s00259-005-1780- 5. 3. 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.

U.S. Provisional Application filed 21 Apr 2006 (HHS Reference No. E-156-2006/0-US-01) Inventors: Lisheng Cai (NIMH), Victor Pike (NIMH), and Robert Innis (NIMH)

Licensees sought: 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.