Synthesis of 3H-labeled N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) and its interaction with mice striatal membrane fragments

PE2I is a high-affinity dopamine transporter (DAT) ligand that exhibits high selectivity for the DAT over the serotonin (5-HTT) and norephinephrine transporter (NET) making its carbon-11 and iodine-125 labeled forms very useful for quantification of DAT binding sites in vivo. In this paper, we reported the synthesis of tritium-labeled PE2I, as well as improvements in the preparation of its acid precursor and PE2I itself with significant improvement in the total yield compared to previously published results. The new radioligand was evaluated as a tool for assessing DAT binding sites in vitro. The radioligand binding to mice striatal membranes demonstrated a homogeneous population of DAT binding sites with the Kd value 9 nM.