RADIOSYNTHESIS OF [C-11] LU-29-024 - A POTENTIAL RADIOTRACER FOR 5HT(2) RECEPTORS PET STUDIES

For mapping 5-HT2 receptors in the central nervous system with positro n emission tomography (PET), 2,5-dimethyl-3- (4 phenyl)-1-(1-[C-11]met hyl-4-piperidinyl)-1H-indole ([C-11]Lu29-024) has been prepared. The p recursor for the radiosynthesis of [C-11]Lu29-024 was obtained in an o verall yield of 53% by a convenient five-step synthesis; its reaction with [C-11]methyl iodide afforded [C-11]Lu29-024 in 35-50% radiochemic al yield (decay corrected) in 45 to 50 min with a specific radioactivi ty ranging from 11 to 15 GBq/mu mol. Following IV injections into rats , the analysis of plasma samples showed that the metabolism of [C-11]L u29-024 was rapid and extensive (60% of the original tracer was metabo lized at 40 min). In contrast, only unmetabolized [C-11]Lu29-024 could be detected in brain tissue. These biological results suggest that la beled metabolites have no access to brain tissue and further propose [ C-11]Lu29-024 as an interesting tool for PET studies of brain 5HT(2) r eceptors. NUCL MED BIOL 25;6:517-522, 1998. (C) 1998 Elsevier Science Inc.