Positron emission tomography of 5-HT transporter sites in the baboon brain with [¹¹C]McN5652

[¹¹C]McN5652 is a new radioligand specific for 5-hydroxytryptamine (5-HT; serotonin) transporters. In this study we used [¹¹C]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 ¹¹C-labeled (+)-McN5652([¹¹C](+)McN5652), then with pharmacologically inactive enantiomer ¹¹C-labeled (-)-McN5652 ([¹¹C](-)McN5652); two animals received a third study with [¹¹C](+)McN5652 after pretreatment with the specific 5-HT uptake site inhibitor fluoxetine (5 mg/kg). Initial uptake into the brain was similar for both [¹¹C](+)McN5652 and [¹¹C](-)McN5652. At later times (45-120 min after injection), only [¹¹C](+)McN5652 showed a distribution characteristic for 5-HT uptake sites. In contrast, in studies with [¹¹C](-)McN5652 and in those with [¹¹C](+)McN5652 after 5-HT uptake site blockade with fluoxetine, ¹¹C radioactivity concentrations were significantly lower and the distribution pattern was relatively even. The differences between [¹¹C](+)-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 [¹¹C](+)McN5652 is suitable for PET imaging of 5-HT uptake sites in primate brain.