[11C]S21007, a putative partial agonist for 5-HT3 receptors PET studies. Rat and primate in vivo biological evaluation.
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.
Besret
L
L
CEA/DSV/DRM GDM-TEP, INSERM U320, Université de Cean, Centre CYCERON, France. besret@cyceron.fr
Dauphin
F
F
Guillouet
S
S
Dhilly
M
M
Gourand
F
F
Blaizot
X
X
Young
A R
AR
Petit-Taboué
M C
MC
Mickala
P
P
Barbelivien
A
A
Rault
S
S
Barré
L
L
Baron
J C
JC
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
D002250:Carbon Radioisotopes; D010879:Piperazines; D011719:Pyrazines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; C106046:S 21007; D017366:Serotonin Receptor Agonists