title: Radiosynthesis of [18F]Lu29-024: a potential PET ligand for brain imaging of the serotonergic 5-HT2 receptor.
abstract: 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 nanomolar 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 followed by a good brain uptake, no brain labeled metabolites but no specific, 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 with a radioactive emitter with a longer half-life than that of carbon-11, could be useful for the quantification of 5HT2A receptors. For these reasons, we chose to label this compound, bearing a fluorine atom, with [18F]fluoride, in order to perform rat studies over a more prolonged time-scale. The precursor for the radiosynthesis of [18F]Lu29-024 was obtained in an overall yield of 20% by a multi-step synthesis including an acetonylation reaction followed by a Fisher indole reaction. The radiotracer was prepared by an aromatic substitution with activated [18F]fluoride followed by a decarbonylation reaction that employed Wilkinson's catalyst. The radiosynthesis of [18F]Lu29-024 required approximatively 110 min with an overall radiochemical yield of 20-35% and specific activities of 37GBq/micromol. Fluorine-labeled 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.
authors.affiliation: GDM-TEP, LRA10V-UPRES EA 2609, Université de Caen CEA/DSV, France.
authors.forename: F
authors.initials: F
authors.lastname: Sobrio
authors.forename: M
authors.initials: M
authors.lastname: Amokhtari
authors.forename: F
authors.initials: F
authors.lastname: Gourand
authors.forename: M
authors.initials: M
authors.lastname: Dhilly
authors.forename: F
authors.initials: F
authors.lastname: Dauphin
authors.forename: L
authors.initials: L
authors.lastname: Barré
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001923:Brain Chemistry; D002247:Carbon Isotopes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis*; D007553:Isotope Labeling; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000032:analysis*; D014055:Tomography, Emission-Computed
chemical_list: D002247:Carbon Isotopes; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D007211:Indoles; D008024:Ligands; C115517:Lu29-024; D010880:Piperidines; D011985:Receptors, Serotonin