SYNTHESIS AND BIODISTRIBUTION OF ETRAHYDRO-1-NAPHTALENYL)PROPYL]-4-PHENYLPIPERAZINE (PNU-157760), A PUTATIVE RADIOLIGAND FOR 5-HT1A RECEPTORS

Racemic etrahydro-1-naphtalenyl)propyl]-4-phenylpiperazine (PNU-157760 ) was labeled with carbon-11 (t(1/2) = 20.4 min) as a putative radioli gand for the noninvasive assessment of 5-HT1A receptors in vivo with p ositron emission tomography (PET). The radiochemical synthesis consist ed of O-methylation of desmethyl precursor with [C-11]methyl iodide in the presence of potassium tert-butoxide in DMF. The desmethyl precurs or for the radiosynthesis of [C-11]PNU-157760, was prepared by a conve nient one-step demethylation of PNU-157760 with boron tribromide. 5-me thoxy-1,2,3,4-tetrahydro-1-naphtalenyl)propyl] with >99% radiochemical purity was obtained in 30 min with a radiochemical yield of 10 +/- 5% (EOS, nondecay corrected) and a specific radioactivity of 2.5 +/- 1 C i/mu mol. Biodistribution studies in rats showed that [C-11]PNU-157760 readily crosses the blood-brain barrier with a maximum of brain uptak e at 30 min after injection; however, the low specific-to-nonspecific binding ratio in vivo as evidenced by the low hippocampus/cerebellum u ptake ratio (1.17 at 60 min postinjection) does not make [C-11]PNU-157 760 a promising radioligand for serotonin 5-HT1A receptors. (C) 1998 A cademic Press