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(11CMcN5652), then with pharmacologically inactive enantiomer 11C-labeled (-)-McN5652 (11CMcN5652); two animals received a third study with 11CMcN5652 after pretreatment with the specific 5-HT uptake site inhibitor fluoxetine (5 mg/kg). Initial uptake into the brain was similar for both 11CMcN5652 and 11CMcN5652. At later times (45-120 min after injection), only 11CMcN5652 showed a distribution characteristic for 5-HT uptake sites. In contrast, in studies with 11CMcN5652 and in those with 11CMcN5652 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 11CMcN5652 is suitable for PET imaging of 5-HT uptake sites in primate brain.