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

Journal Article (Journal Article)

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 radiofluorinated 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. 110 min. 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 K(d) value of 28 pM, consistent with the K(i) value of 25 pM, derived previously for unlabeled 1 in competition assays with (±)-[3H]epibatidine.

Full Text

Duke Authors

Cited Authors

  • Koren, AO; Horti, AG; Mukhin, AG; Gündisch, D; Dannals, RF; London, ED

Published Date

  • January 1, 2000

Published In

Volume / Issue

  • 43 / 5

Start / End Page

  • 413 - 423

International Standard Serial Number (ISSN)

  • 0362-4803

Digital Object Identifier (DOI)

  • 10.1002/(SICI)1099-1344(200004)43:5<413::AID-JLCR326>3.0.CO;2-1

Citation Source

  • Scopus