FENFLURAMINE-INDUCED LOSS OF SEROTONIN TRANSPORTERS IN BABOON BRAIN VISUALIZED WITH PET

The present study sought to determine whether or not Positron Emission Tomography (PET) with the newly developed positron emitting serotonin (5-HT) transporter ligand, (+)[C-11]McN-5652, could be used to detect fenfluramine-induced 5-HT neurotoxicity in the brain of living primat es (baboons). Six PET imaging studies were performed: three before tre atment with fenfluramine (5 mg/kg, s.c., twice daily for 4 days) and t hree after (18, 45, and 81 days after treatment). The dose of fenflura mine used in this study (5 mg/kg) is known to produce 5-HT neurotoxici ty in primates, and to be approximately two times higher than a dose o f fenfluramine reported to produce small and inconsistent weight loss in baboons (2 mg/kg). Following fenfluramine treatment, marked lasting reductions in regional brain specific binding of(+)[C-11]McN-5652 wer e found by means of PET. Findings with PET corresponded well with post -mortem neurochemical findings indicative of serotonergic neurotoxicit y (lasting depletions of regional brain 5-HT, 5-HIAA, and 5-HT uptake sites). These results suggest that PET imaging with (+)[C-11]McN-5652 will be useful for evaluating the 5-HT neurotoxic potential of fenflur amine and related drugs in living humans. (C) 1996 Wiley-Liss, Inc.