Synthesis of [18F]norchlorofluoroepibatidine and its N-methyl derivative: New PET ligands for mapping nicotinic acetylcholine receptors

Y. S. Ding, F. Liang, J. S. Fowler, M. J. Kuhar, F. I. Carroll

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Fluorine-18 labeled norchlorofluoroepibatidine (NFEP), a high-affinity nicotinic acetylcholine receptor ligand, was prepared by a one-pot, two-step synthesis: nucleophilic heteroaromatic substitution of a tert-Boc protected precursor (7-tert-butyloxycarbonyl-exo-2-(2'-N,N,N-trimethylammonium-5'-pyridinyl)-7 -azabicyclo[2.2.1]heptane iodide) using no-carrier-added [18F]fluoride followed by deprotection with trifluoroacetic acid. Subsequent reductive N-methylation with formaldehyde and sodium cyanoborohydride afforded fluorine-18 labeled N-methyl-norchlorofluoroepibatidine (N-methyl-NFEP). The unusually high radiochemical yield for the first step (70%) and the quantitative conversions in the deprotection and N-methylation steps afforded overall radiochemical yields of 55-65% (decay corrected based on starting [18F]fluoride) for [18F]NFEP (synthesis time 65 min) and 45-55% for [18F]N-methyl-NFEP (synthesis time 75 min), with a specific activity of 2-9 Ci/μmole (EOB).

Original languageEnglish
Pages (from-to)827-832
Number of pages6
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume39
Issue number10
DOIs
StatePublished - Oct 1997
Externally publishedYes

Keywords

  • Epibatidine
  • Fluorine-18
  • Nicotinic acetylcholine receptors
  • Positron emission tomography

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