Positron Emission Tomography of 5-HT Transporter Sites in the Baboon Brain with [11C]McN5652

[C]McN5652 is a new radioligand specific for 5-hydroxytryptamine (5-HT; serotonin) transporters. In this study we used [ 11 C]McN5652 to image the 5-HT transporter sites in baboon brain by positron emission tomography (PET). Dynamic PET studies were performed in three Papio anubis baboons. The animals were injected intravenously first with 11 C-labeled (+)-McN5652([ 11 C](+)McN5652), then with pharmacologically inactive enantiomer 11 C-labeled (–)-McN5652 ([ 11 C](–)McN5652); two animals received a third study with [ 11 C](+)McN5652 after pretreatment with the specific 5-HT uptake site inhibitor fluoxetine (5 mg/kg). Initial uptake into the brain was similar for both [ 11 C](+)McN5652 and [ 11 C](–)McN5652. At later times (45–120 min after injection), only [ 11 C](+)McN5652 showed a distribution characteristic for 5-HT uptake sites. In contrast, in studies with [ 11 C](–)McN5652 and in those with [ 11 C](+)McN5652 after 5-HT uptake site blockade with fluoxetine, 11 C radioactivity concentrations were significantly lower and the distribution pattern was relatively even. The differences between [ 11 C](+)-and (–)McN5652 were calculated for the time interval 95–125 min postinjection and used to estimate specific binding. Specific binding correlated well ( r = 0.95, p < 0.001) with the known density of 5-HT uptake sites in human brain. These results indicate that [ 11 C](+)McN5652 is suitable for PET imaging of 5-HT uptake sites in primate brain.