[C-11] S21007, A PUTATIVE PARTIAL AGONIST FOR 5-HT3 RECEPTORS PET STUDIES - RAT AND PRIMATE IN-VIVO BIOLOGICAL EVALUATION

We recently labeled with carbon-ii, a high affinity, selective, 5-HT3 receptor (5-HT3R) ligand, S21007, for potential positron emission tomo graphy (PET) applications. To evaluate the in vivo binding properties of [C-11]S21007, its brain regional distribution, tissue and pla sma p harmacokinetics and plasma metabolisation were characterized. To circu mvent the problem of highly discrete brain localization of the 5-HT3R (area postrema, hippocampus), we designed an original approach combini ng high-resolution imaging techniques (ex vivo phosphor plate autoradi ography and MRI-guided coronal PET in the rat and baboon, respectively ). After i.v. injection of trace amounts of [C-11]S21007 to rats, phos phorimager autoradiography failed to reveal in vivo specific binding t o, nor selectivity for 5-HT3R-rich areas. PET studies in the baboon sh owed consistent results, i.e., there was no selective accumulation of [C-11]S21007 in the area postrema or hippocampus, and neither displace ment nor presaturation with cold S21007 resulted in significant change s in tissue distribution or kinetics of [C-11]S21007.