title: Fenfluramine-induced loss of serotonin transporters in baboon brain visualized with PET.
abstract: 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.
authors.affiliation: Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: Z
authors.initials: Z
authors.lastname: Szabo
authors.forename: W B
authors.initials: WB
authors.lastname: Mathews
authors.forename: P A
authors.initials: PA
authors.lastname: Finley
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: B
authors.initials: B
authors.lastname: Callahan
authors.forename: G
authors.initials: G
authors.lastname: Hatzidimitriou
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: G A
authors.initials: GA
authors.lastname: Ricaurte
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010215:Papio; D050486:Serotonin Plasma Membrane Transport Proteins; D014055:Tomography, Emission-Computed
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D005277:Fenfluramine