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

Andrei O. Koren, Andrew G. Horti, Alexey G. Mukhin, Daniela Gündisch, Robert F. Dannals, Edythe D. London

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)413-423
Number of pages11
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Issue number5
StatePublished - Jan 1 2000


  • A-85380
  • Fluorine-18
  • Nicotinic acetylcholine receptors
  • Nucleophilic heteroaromatic substitution
  • Radioligand
  • Receptor binding

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry


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