Synthesis of [F-18]norchlorofluoroepibatidine and its N-methyl derivative: New PET ligands for mapping nicotinic acetylcholine receptors
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-[2.2.1]heptane iodide) using no-carrier-added [F-18]fluoride followed by deprotection with trifluoroacetic acid. Subsequent reductive N-methylation with formaldehyde and sodium cyanoborohydride afforded fluorine-lb 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 [F-18]fluoride) for [F-18]NFEP (synthesis time 65 min) and 45-55% for [F-18]N-methyl-NFEP (synthesis time 75 min), with a specific activity of 2-9 Ci/mu mole (EOB).
Ding, Y. S., Liang, F., Fowler, J. S., Kuhar, M. J., & Carroll, F. (1997). Synthesis of [F-18]norchlorofluoroepibatidine and its N-methyl derivative: New PET ligands for mapping nicotinic acetylcholine receptors. Journal of Labelled Compounds and Radiopharmaceuticals, 39(10), 827-832.