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

A novel positron emission tomography (PET) radiotracer, 6-18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-18F]fluoro-A-85380, 6-18F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-18F]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (Kd 28 pM). In PET studies, 6-18F]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 alpha4beta2 subtype of nAChR. 6-18F]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, 18F]FPH. In contrast to 18F]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.