title: [11C]S21007, a putative partial agonist for 5-HT3 receptors PET studies. Rat and primate in vivo biological evaluation.
abstract: We recently labeled with carbon-11, a high affinity, selective, 5-HT3 receptor (5-HT3R) ligand, S21007, for potential positron emission tomography (PET) applications. To evaluate the in vivo binding properties of [11C]S21007, its brain regional distribution, tissue and plasma pharmacokinetics and plasma metabolisation were characterized. To circumvent the problem of highly discrete brain localization of the 5-HT3R (area postrema, hippocampus), we designed an original approach combining high-resolution imaging techniques (ex vivo phosphor plate autoradiography and MRI-guided coronal PET in the rat and baboon, respectively). After i.v. injection of trace amounts of [11C]S21007 to rats, phosphorimager autoradiography failed to reveal in vivo specific binding to, nor selectivity for 5-HT3R-rich areas. PET studies in the baboon showed consistent results, i.e., there was no selective accumulation of [11C]S21007 in the area postrema or hippocampus, and neither displacement nor presaturation with cold S21007 resulted in significant changes in tissue distribution or kinetics of [11C]S21007.
authors.affiliation: CEA/DSV/DRM GDM-TEP, INSERM U320, Université de Cean, Centre CYCERON, France. besret@cyceron.fr
authors.forename: L
authors.initials: L
authors.lastname: Besret
authors.forename: F
authors.initials: F
authors.lastname: Dauphin
authors.forename: S
authors.initials: S
authors.lastname: Guillouet
authors.forename: M
authors.initials: M
authors.lastname: Dhilly
authors.forename: F
authors.initials: F
authors.lastname: Gourand
authors.forename: X
authors.initials: X
authors.lastname: Blaizot
authors.forename: A R
authors.initials: AR
authors.lastname: Young
authors.forename: M C
authors.initials: MC
authors.lastname: Petit-Taboué
authors.forename: P
authors.initials: P
authors.lastname: Mickala
authors.forename: A
authors.initials: A
authors.lastname: Barbelivien
authors.forename: S
authors.initials: S
authors.lastname: Rault
authors.forename: L
authors.initials: L
authors.lastname: Barré
authors.forename: J C
authors.initials: JC
authors.lastname: Baron
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D008297:Male; D010215:Papio; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011719:Pyrazines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D011719:Pyrazines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; C106046:S 21007; D017366:Serotonin Receptor Agonists