The present study sought to determine whether or not Positron Emission Tomography (PET) with the newly developed positron emitting serotonin (5-HT) transporter ligand, (+)[11C]McN-5652, could be used to detect fenfluramine- induced 5-HT neurotoxicity in the brain of living primates (baboons). Six PET imaging studies were performed: three before treatment with fenfluramine (5 mg/kg, s.c., twice daily for 4 days) and three after (18, 45, and 81 days after treatment). The dose of fenfluramine used in this study (5 mg/kg) is known to produce 5-HT neurotoxicity in primates, and to be approximately two times higher than a dose of 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 (+)[11C]McN-5652 were found by means of PET. Findings with PET corresponded well with post-mortem neurochemical findings indicative of serotonergic neurotoxicity (lasting depletions of regional brain 5-HT, 5-HIAA, and 5-HT uptake sites). These results suggest that PET imaging with (+)[11C]McN- 5652 will be useful for evaluating the 5-HT neurotoxic potential of fenfluramine and related drugs in living humans.
|Original language||English (US)|
|Number of pages||4|
|State||Published - Dec 1996|
- Positron Emission Tomography
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience