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In Vivo Delineation of 5-HT_1A Receptors in Human Brain with [¹⁸F]MPPF

PET Center, Groningen University Hospital, Groningen; Groningen University Institute for Drug Exploration, Groningen, The Netherlands

Serotonin-1A (5-hydroxytryptamine-1A [5-HT_1A]) 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-[¹⁸F]fluorobenzamido]ethylpiperazine ([¹⁸F]MPPF) may be suitable for 5-HT_1A receptor imaging in humans. The aim of this study was to determine if [¹⁸F]MPPF can be used for the quantitative analysis of 5-HT_1A receptor densities in brain regions of healthy human volunteers. Methods: [¹⁵O]H₂O perfusion scanning was performed before intravenous injection of [¹⁸F]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [¹⁸F]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 ¹⁸F, in accordance with known 5-HT_1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT_1A receptor densities. The binding potentials for [¹⁸F]MPPF were 4–6 times lower than those that have been reported for [carbonyl-¹¹C]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY 100635), indicating that [¹⁸F]MPPF has a lower in vivo affinity for 5-HT_1A receptors. Conclusion: These results confirm that [¹⁸F]MPPF can be used for the quantitative analysis of 5-HT_1A 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.

Key Words: human • brain • serotonin-1A receptors • 5-hydroxytryptamine-1A receptors • 4-(2'-methoxyphenyl)-1-[2'-(N-2''-pyridinyl)-p-fluorobenzamido]ethylpiperazine

Received Oct. 12, 1999; revision accepted Mar. 28, 2000.

For correspondence or reprints contact: Jan Passchier, PhD, PET Center, Groningen University Hospital, 9700 RB Groningen, The Netherlands.

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