RT Journal Article
SR Electronic
T1 In Vivo Delineation of 5-HT<sub>1A</sub> Receptors in Human Brain with [<sup>18</sup>F]MPPF
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1830
OP 1835
VO 41
IS 11
A1 Jan Passchier
A1 Aren van Waarde
A1 Remge M. Pieterman
A1 Philip H. Elsinga
A1 Jan Pruim
A1 Harry N. Hendrikse
A1 Antoon T.M. Willemsen
A1 Willem Vaalburg
YR 2000
UL http://jnm.snmjournals.org/content/41/11/1830.abstract
AB 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-[18F]fluorobenzamido]ethylpiperazine ([18F]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [18F]MPPF can be used for the quantitative analysis of 5-HT1A 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-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A 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-HT1A receptors. Conclusion: These results confirm that [18F]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.