Fenfluramine-induced loss of serotonin transporters in baboon brain visualized with PET
✍ Scribed by Ursula Scheffel; Zsolt Szabo; William B. Mathews; Paige A. Finley; Jie Yuan; Brian Callahan; George Hatzidimitriou; Robert F. Dannals; Hayden T. Ravert; George A. Ricaurte
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 868 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0887-4476
No coin nor oath required. For personal study only.
✦ Synopsis
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 mgkg, 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 mgkg) 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 mgkg). Following fenfluramine treatment, marked lasting reductions in regional brain specific binding of (+ )["C]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. o 1996 Wiley-Liss, Inc.