11C-labeling and preliminary evaluation of vortioxetine as a PET radioligand

Vortioxetine is a new multi-modal drug against major depressive disorder with high affinity for a range of different serotonergic targets in the CNS. We report the 11C-labeling of vortioxetine with [11C]MeI using a Suzuki-protocol that allows for the presence of an unprotected amine. Preliminary evaluation of [11C]vortioxetine in a Danish Landrace pig showed rapid brain uptake and brain distribution in accordance with the pharmacological profile, all though an unexpected high binding in cerebellum was also observed. [11C]vortioxetine displayed slow tracer kinetics with peak uptake after 60 min and with limited wash-out from the brain. Further studies are needed but this radioligand may prove to be a valuable tool in unraveling the clinical effects of vortioxetine.