Synthesis and biological evaluation of a new series of nicotinic acetylcholine receptor (nAChR) ligands for positron emission tomography (PET)

MEDI 490

Yongjun Gao, ygao5@jhmi.edu1, Hayden T Ravert1, Daniel Holt1, John Hilton1, Chris Endres1, Mohab Alexander2, Anil Kumar1, Arman Rahmim1, Hiroto Kuwabara1, Dean F. Wong1, Robert F. Dannals1, and Andrew G. Horti1. (1) Department of Radiology, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205, (2) Department of Radiology, Johns Hopkins University School of Medicine
The most abundant subtype of cerebral nicotinic acetylcholine receptors, 􊨴-nAChRs play a critical role in various brain functions and pathological states. Imaging agents suitable for visualization and quantification of the 􊨴-nAChRs by positron emission tomography (PET) techniques would present unique opportunities to define the function and pharmacology of the nAChRs in the living human brain. They would therefore provide a useful tool to diagnose and monitor response to therapy in various diseases. In this study, we report the synthesis, nAChR binding affinity, and pharmacological properties of a new series of 3-pyridyl ether analogs of A-85380. Some of these nAChR ligands were radiolabeled with positron-emitting isotope 11C and evaluated in animal studies as potential PET radiotracers for imaging of cerebral nAChRs with improved brain kinetics compared with 2-[18F]-fluoro-A-85380, the radiotracer for PET imaging of 􊨴-nAChRs in humans.
 

General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006