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 [¹¹C](+)McN5652 (the (+) enantiomer of trans‐l,2,3,5,6,10β‐hexahydro‐6‐[4‐(methylthio) phenyl]pyrrolo‐[2,1‐a] ‐isoquinoline), 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 [¹¹C](+)McN5652 binding, additional images were obtained in the same subjects after injection of [¹¹C](−)McN5652, the pharmacologically inactive enantiomer, and, in two of the subjects, with [¹¹C](+)McN5652 after pretreatment with the 5‐HT uptake site blocker fluoxetine. Highest accumulation of [¹¹C](+)McN5652 was observed in the midbrain, putamen, caudate nucleus, hypothalamus, and thalamus, regions known to contain high densities of 5‐HT transporters. In these areas [¹¹C](+)McN5652 concentrations rose steadily over 120 min. In contrast, with [¹¹C](−)McN5652 and when the [¹¹C](+)McN5652 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 [¹¹C](+)McN5652, there is specific binding. In the cerebellum, a region relatively void of 5‐HT transporters, both [¹¹C](+)McN5652 with and without fluoxetine block and [¹¹C](−)McN5652 were released at approximately the same rate. The results of the studies indicate that [¹¹C](+)McN5652 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. © 1995 Wiley‐Liss, Inc.