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, t wo-step synthesis: nucleophilic heteroaromatic substitution of a tert- Boc protected precursor N-trimethylammonium-5'-pyridinyl)-7-[2.2.1]hep tane iodide) using no-carrier-added [F-18]fluoride followed by deprote ction with trifluoroacetic acid. Subsequent reductive N-methylation wi th formaldehyde and sodium cyanoborohydride afforded fluorine-lb label ed 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 over all 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).