Tissue distribution, autoradiography, and metabolism of 4-(2 '-methoxyphenyl)-1-[2 '-[N-(2 ''-pyridinyl)-p-[F-18]fluorobenzamido]ethyl]piperazine (p-[F-18]MPPF), a new serotonin 5-HT1A antagonist for positron emission tomography: An in vivo study in rats

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2' -[N-(2"-pyridinyl)-p-[F- 18]fluorobenzamido]ethyl]piperazine (p-[F-18]MPPF), a new serotonin 5-HT1A antagonist, was studied in awake, freely moving rats. Biodistribution studi es showed that the carbon-fluorine bond was stable in vivo, that this compo und was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great qu antity of highly polar metabolites found in plasma did not contribute to th e small amounts of metabolites found in hippocampus, frontal cortex, and ce rebellum. Ex vivo p-[F-18]MPPF and in vitro 8-hydroxy-2-(di-n-[H-3]propylam ino)tetralin autoradiography were compared both qualitatively and quantitat ively. Qualitative evaluation proved that the same brain regions were label ed and that the p-[F-18]MPPF labeling is (a) in total agreement with the kn own distribution of 5-HT1A receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in v ivo labeling pattern obtained with p-[F-18]MPPF cannot be explained by diff erences in regional blood flow, capillary density, or permeability. The 5-H T1A specificity of p-[F-18]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to eva luate parameters characterizing 5-HT1A binding sites in the brain.