Fenfluramine-Induced Serotonin Release Decreases [11C]AZ10419369 Binding to 5-HT1B-Receptors in the Primate Brain

The need for positron emission tomography (PET)-radioligands that are sensitive to changes in endogenous serotonin (5-HT) levels in brain is recognized in experimental and clinical psychiatric research. We recently developed the novel PET radioligand [C-11]AZ10419369 that is highly selective for the 5-HT1B receptor. In this PET-study in three cynomolgus monkeys, we examined the sensitivity of [C-11]AZ10419369 to altered endogenous 5-HT levels. Fenfluramine-induced 5-HT release decreased radioligand binding in a dose-dependent fashion with a regional average of 27% after 1 mg/kg and 50% after 5 mg/kg. This preliminary study supports that [C-11]AZ10419369 is sensitive to endogenous 5-HT levels in vivo and may serve as a tool to examine the pathophysiology and treatment of major psychiatric disorders. Synapse 64:573-577, 2010. (C) 2010 Wiley-Liss, Inc.