Synthesis and initial in vitro characterization of 6-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine, a high-affinity radioligand for central nicotinic acetylcholine receptors

6-[F-18]Fluora-3-(2(S)-azetidinylmethoxy)pyridine ([F-18](1) under bar), a novel analogue of the high-affinity nicotinic acetylcholine receptor ligand , A-85380, was prepared by a two-step procedure from an appropriate nitro p recursor. In the first step, a Kryptofix 222-assisted F-18 nucleophilic het eroaromatic substitution in 6-nitro-3-((1-tert-butoxycarbonyl-2(S)-azetidin yl)methoxy)pyridine provided a radio-fluorinated Boc-protected intermediate . Subsequent acidic deprotection of the intermediate gave [F-18](1) under b ar with an overall radiochemical yield of 8 to 12% (non-decay-corrected). T he typical synthesis time was ca. 110 min. Specific radioactivity of the fi nal product ranged from 1000 to 4500 mCi/mu mol, as calculated at the end-o f-synthesis. III vitro studies demonstrated that the novel radioligand boun d to a single population of sites in rat brain membranes, presumably, to th e alpha 4 beta 2 subtype of nicotinic acetylcholine receptor. This binding was characterized by a K-d value of 28 pM, consistent with the K-i value of 25 pM, derived previously for unlabeled (1) under bar in competition assay s with (+/-)-[H-3]epibatidine.