Synthesis,radiolabeling and preliminary in vivo evaluation of [18F]FE-PE2I,a new probe for the dopamine transporter

A new dopamine transporter (DAT) ligand, (E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4′-methyl-phenyl) nortropane (FE-PE2I, 6), derived from PE2I (1), was prepared and found to be a potent inhibitor of rodent DAT in vitro. Compound 6 was radiolabelled with fluorine-18 (t_1/2 = 109.8 min) for PET studies in monkeys. In vivo PET measurements showed a regional distribution in brain that corresponds to the known distribution of DAT. This binding was specific, reversible and the kinetics of ¹⁸F]6 binding in brain were faster than for its lead compound, ¹¹C]1. The possible presence of a hydroxymethyl-radiometabolite formed by oxidation in the 3β-benzylic position of ¹⁸F]6 warrants further detailed evaluation of the metabolism of ¹⁸F]6. ¹⁸F]6 is a potential radioligand for imaging DATs in the human brain with PET.