6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors

A novel positron emission tomography (PET) radiotracer, 6-[F-18]fluoro-3-(2(S)-azetidinyl-methoxy)pyridine (6-[F-18]fluoro-A-85380, 6-[F-18]FA) was synthesized by a no-carrier-added fluorination, In 6-[F-18]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (K-d 28 PM). In PET studies, 6-[F-18]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the a,Pz subtype of nAChR, 6-[F-18]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [F-18]FPH. In contrast to [F-18]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain. Published by Elsevier Science Inc.