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A novel radioligand for positron emission tomography (PET) imaging of serotonin 5-HT1B receptors, [11C]AZ10419369, has been recently described. In this study, the potential for quantitative analysis of [11C]AZ10419369 binding to central 5-HT1B receptors was evaluated in human subjects. PET measurements were performed after injection of [11C]AZ10419369 in 10 subjects. Data were analyzed with kinetic modeling and linear graphical analysis using the arterial plasma as input function, and with reference tissue models using cerebellar cortex as the reference region. Binding of [11C]AZ10419369 was highest in pallidum, ventral striatum, and occipital cortex and lowest in cerebellum. The percentage of unchanged radioligand in plasma was 97% to 99%, indicating that no significant amounts of radioactive metabolites were formed during the time of analysis. Time–activity curves of [11C]AZ10419369 could be described with both one-tissue compartment (1-TC) and two-tissue compartment (2-TC) models in the majority of subjects. The 2-TC model failed to deliver reasonable estimates of the kinetic parameters. However, stable estimates of binding potential ( BPND) were obtained by constraining K1/ k2 to the distribution volume obtained with the 1-TC model in the cerebellar cortex. BPND values estimated with reference tissue models were correlated with the corresponding values obtained with kinetic modeling. The findings support the use of reference tissue models in applied clinical studies with [11C]AZ10419369.

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 [(11)C]AZ10419369 that is highly selective for the 5-HT(1B) receptor. In this PET-study in three cynomolgus monkeys, we examined the sensitivity of [(11)C]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 [(11)C]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.