Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652.

This paper presents the first Positron Emission Tomography (PET) images of the serotonin (5-hydroxytryptamine, 5-HT) transporter in the living human brain. PET imaging was performed in three healthy subjects after administration of 11CMcN5652 (the (+) enantiomer of trans-1,2,3,5,6,10 beta-hexahydro- 6-[4-(methylthio) phenyl]pyrrolo-[2,1-a] -isoquinolone), a radioligand previously shown to selectively label the 5-HT transporter in vivo in the mammalian (mouse and baboon) brain. To demonstrate the specificity of 11CMcN5652 binding, additional images were obtained in the same subjects after injection of 11CMcN5652, the pharmacologically inactive enantiomer, and, in two of the subjects, with 11CMcN5652 after pretreatment with the 5-HT uptake site blocker fluoxetine. Highest accumulation of 11CMcN5652 was observed in the midbrain, putamen, caudate nucleus, hypothalamus, and thalamus, regions known to contain high densities of 5-HT transporters. In these areas 11CMcN5652 concentrations rose steadily over 120 min. In contrast, with 11CMcN5652 and when the 11CMcN5652 binding was inhibited with fluoxetine, radioactivity concentrations declined after reaching a maximum (at 20 to 30 min). Inhibition studies with fluoxetine suggest that only with 11CMcN5652, there is specific binding. In the cerebellum, a region relatively void of 5-HT transporters, both 11CMcN5652 with and without fluoxetine block and 11CMcN5652 were released at approximately the same rate. The results of the studies indicate that 11CMcN5652 labels 5-HT transporter sites in the human brain. Quantitative PET imaging studies with this new tracer should provide valuable information on the status of these sites in health and disease.