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

6‐[18F]Fluoro‐3‐(2(S)‐azetidinylmethoxy)pyridine ([18F]1), a novel analogue of the high‐affinity nicotinic acetylcholine receptor ligand, A‐85380, was prepared by a two‐step procedure from an appropriate nitro precursor. In the first step, a Kryptofix 222‐assisted 18F nucleophilic heteroaromatic substitution in 6‐nitro‐3‐((1‐tert‐butoxycarbonyl‐2(S)‐azetidinyl)methoxy)pyridine provided a radio‐fluorinated Boc‐protected intermediate. Subsequent acidic deprotection of the intermediate gave [18F]1 with an overall radiochemical yield of 8 to 12% (non‐decay‐corrected). The typical synthesis time was ca. Specific radioactivity of the final product ranged from 1000 to 4500 mCi/μmol, as calculated at the end‐of‐synthesis. In vitro studies demonstrated that the novel radioligand bound to a single population of sites in rat brain membranes, presumably, to the α4β2 subtype of nicotinic acetylcholine receptor. This binding was characterized by a Kd value of 28 pM, consistent with the Ki value of 25 pM, derived previously for unlabeled 1 in competition assays with (±)‐[3H]epibatidine Copyright © 2000 John Wiley & Sons, Ltd.