In vivo delineation of 5-HT(1A) receptors in human brain with [18F]MPPF

J. Passchier*, A. Van Waarde, R. M. Pieterman, P. H. Elsinga, J. Pruim, H. N. Hendrikse, A. T.M. Willemsen, W. Vaalburg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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]ethylpi perazine ([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 ) cyclohexane-carboxamide (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.

Original languageEnglish
Pages (from-to)1830-1835
Number of pages6
JournalJournal of Nuclear Medicine
Issue number11
Publication statusPublished - 22 Nov 2000

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