In vivo delineation of 5-HT1A receptors in human brain with [F-18]MPPF

Serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors have been reported to play an important role in the pathophysiology of a variety of psychiatric and neurodegenerative disorders. Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2 " -pyridinyl)-p-[F-18]fluorobenzamido]ethylpiperazine ([F-18]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [F-18]MPPF can be used for the quantitative analysis of 5-HT1A receptor densities in brain regions of healthy human volunteers. Methods: [O-15]H2O perfusion scanning was performed before intravenous injection of [F-18]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [F-18]MPPF were determined by high-performance liquid chromatography. Binding potentials were calculated using the metabolite-corrected arterial input function and a linear graphic method (Logan-Patlak analysis). Results: The highest levels of radioactivity were observed in the medial temporal cortex, especially in the hippocampal area. In contrast, the cerebellum and basal ganglia showed low uptake of F-18, in accordance with known 5-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A receptor densities. The binding potentials for [F-18]MPPF were 4-6 times lower than those that have been reported for [carbonyl-C-11]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexane-carboxamide (WAY 100635), indicating that [F-18]MPPF has a lower in vivo affinity for 5-HT1A receptors. Conclusion: These results confirm that [F-18]MPPF can be used for the quantitative analysis of 5-HT1A receptor distribution in the living human brain. The:rapid dissociation from the receptor makes this ligand a possible candidate to monitor changes in endogenous serotonin levels.