title: Tissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.
abstract: The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT(1A) receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[(18)F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT(1A) binding sites in the brain.
authors.affiliation: Cyclotron Research Center, Liège University, Liège, Belgium. CERMEP, Lyon, France. CNRS-UCBL ERS 2022, Lyon, France. Alain.Plenevaux@ulg.ac.be
authors.forename: A
authors.initials: A
authors.lastname: Plenevaux
authors.forename: D
authors.initials: D
authors.lastname: Weissmann
authors.forename: J
authors.initials: J
authors.lastname: Aerts
authors.forename: C
authors.initials: C
authors.lastname: Lemaire
authors.forename: C
authors.initials: C
authors.lastname: Brihaye
authors.forename: C
authors.initials: C
authors.lastname: Degueldre
authors.forename: D
authors.initials: D
authors.lastname: Le Bars
authors.forename: D
authors.initials: D
authors.lastname: Comar
authors.forename: J
authors.initials: J
authors.lastname: Pujol
authors.forename: A
authors.initials: A
authors.lastname: Luxen
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics; D000631:Aminopyridines / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D009928:Organ Specificity; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000032:analysis / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012044:Regression Analysis; D012702:Serotonin Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014316:Tritium
chemical_list: D000631:Aminopyridines; D005462:Fluorine Radioisotopes; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D014316:Tritium; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine