IN-VIVO BIODISTRIBUTION OF A RADIOTRACER FOR IMAGING SEROTONIN-1A RECEPTOR-SITES WITH PET - [C-11] LY274601

LY274601 R-(+)-8-thiomethyl-2-(di-n-propyl-amino)tetralin], a full ago nist of the 5-HT1A receptor with high affinity and selectivity, was la beled with C-11 and H-3, and its in vivo behavior was studied to evalu ate [C-11]LY274601 as a PET radiotracer for imaging 5-HT1A receptor si tes in living brain. Following intravenous tail injection into mice, [ C-11]LY274601 showed high blood-brain barrier permeability and accumul ated in regions known to have high densities of 5-HT1A receptor sites such as the brain stem including the raphe nuclei. The binding of the radiotracer in target tissues is blocked by pre-injection of the 5-HT1 A receptor selective ligand 8-OH-DPAT (1 mg/kg, sc), suggesting that t he binding is specific to 5-HT1A receptor sites. Using ex vivo autorad iography, the target tissues such as hippocamous CA1-4 fields, pirifor m cortex, dorsal raphe nucleus and lateral septum were visualized as h ot spots. These tissues were observed to have binding 2 - 2.7 times gr eater than the cerebellum. The distribution of the radiotracer agrees well with the distribution of 5-HT1A receptors revealed by in vitro au toradiography with [H-3]8-OH-DPAT. However, the radiotracer was metabo lized quickly and cleared from target tissues with a half life of appr oximately 15 min. [C-11]LY274601 showed high non-specific binding in r egions with low number of 5-HT1A receptor sites such as cerebellum.