A novel positron emission tomography (PET) radiotracer, 6-[18F]fluoro- 3-(2(S)-azetidinyl-methoxy)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 (K(d) 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 α4β2 subtype of nAChR. 6-[18F]FA exhibited a target-to-non-target ratio (estimated as radio- activity 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.
- 6-[F]fluoro-3-(2(S)azetidinyl-methoxy)pyridine (6-[F]fluoro- A-85380, 6-[F]FA)
- Nicotinic acetylcholine receptor
- Positron emission tomography (nAChRs)
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)