In Vitro And In Vivo Evaluation Of N-{2-[4-(3-Cyanopyridin-2-Yl)Piperazin-1-Yl]Ethyl}-3-[C-11]Methoxybenzam Ide, A Positron Emission Tomography (Pet) Radioligand For Dopamine D-4 Receptors, In Rodents

The D-4 dopamine receptor belongs to the D-2-like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D-4 receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D-4 receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high-affinity D-4 receptor-selective ligand N-{2-[4-(3-cyanopyridin-2-yl) piperazin-1-yl] ethyl}-3-[C-11] methoxybenzamide ([C-11]2) in rat. The results provide new insights on the in vitro properties that a brain PET dopamine D-4 radioligand should possess in order to have improved in vivo utility in rodents.