Synthesis of S-([¹⁸F]fluoromethyl)-(+)-McN5652 as a potential PET radioligand for the serotonin transporter

The present study describes the synthesis of the [¹⁸F]fluoromethyl analogue of (+)-McN5652 ([¹⁸F]FMe-McN) as a new potential tracer for the serotonin transporter. In vitro binding studies have shown that FMe-McN displays only slightly lower affinity for the serotonin transporter (K_i=2.3 ± 0.1 nM) than (+)-McN5652 (K_i=0.72 ± 0.2 nM). The radiofluorinated tracer [¹⁸F]FMe-McN was prepared by reaction of normethyl (+)-McN5652 with the fluoromethylation agent [¹⁸F]bromofluoromethane in an overall radiochemical yield of 5 ± 1% (decay-corrected, related to [¹⁸F]fluoride) and with high specific radioactivity (200 - 2000 GBq/µmol at the end of synthesis).