Fluorine-18-labeled tropane analogs for PET imaging studies of the dopamine transporter.

A series of PET imaging studies were conducted with two fluorine-18-labeled tropane analoges, [(18)F](+)-FTT and [(18)F](+)-FCT. Both compounds possessed a high affinity and selectivity for the dopamine transporter and had a higher accumulation in the basal ganglia, a brain region having a high density of the dopamine transporter (DAT) than the cerebellum, a reference region devoid of dopaminergic terminals. [(18)F](+)-FCT had a higher brain uptake and more suitable basal ganglia:cerebellum (BG:Cb) ratio than [(18)F](+)-FTT. [(18)F](+)-FCT also displayed reversible binding kinetics in vivo, indicating that the measurement of DAT density in vivo with PET will be relatively insensitive to changes in cerebral blood flow that can occur as a consequence of disease or prolonged cocaine abuse. The uptake of [(18)F](+)-FCT was also displaced by an intravenous injection of cocaine (1.0 mg/kg), which is consistent with the labeling of the DAT in vivo by this radiotracer. These data suggest that [(18)F](+)-FCT may be a suitable radiotracer for studying DAT function in vivo with PET.