Radiosynthesis of [F-18]Lu29-024: A potential PET ligand for brain imagingof the serotonergic 5-HT2 receptor

In a previous work, Lu29-024 (2,5-dimethyl-3-(4-fluorophenyl)-1-(1-methyl-4 -piperidinyl)-1H-indole), a selective 5-HT2A receptor antagonist with nanom olar affinity and high selectivity, was labeled with carbon-11 to evaluate its behavior as a potential PET ligand for the serotonergic 5-HT2A receptor in the central nervous system. Administration of this tracer to rats was f ollowed by a good brain uptake, no brain labeled metabolites but no specifi c, regio-selective, binding at 20 and 40 min post injection. Despite this, the data noted at 20 and 40 min suggest that this tracer, if associated wit h a radioactive emitter with a longer half-life than that of carbon-11, cou ld be useful for the quantification of 5HT(2A) receptors. For these reasons , we chose to label this compound, bearing a fluorine atom, with [F-18]fluo ride, in order to perform rat studies over a more prolonged time-scale. The pre cursor for the radiosynthesis of [F-18]Lu29-024 was obtained in an ove rall yield of 20% by a multi-step synthesis including an acetonylation reac tion followed by a Fisher indole reaction. The radiotracer was prepared by an aromatic substitution with activated [F-18]fluoride followed by a decarb onylation reaction that employed Wilkinson's catalyst. The radiosynthesis o f [F-18]Lu29-024 required approximatively 110 min with an overall radiochem ical yield of 20-35% and specific activities of 37GBq/mu mol. Fluorine-labe led Lu29-024 may thus be envisaged as a potentially useful PET tracer that can be applied to a wide range of neurological and psychiatric diseases. (C ) 2000 Elsevier Science Ltd. All rights reserved.