title: Radiosynthesis of carbon-11 and fluorine-18 labelled radiotracers to image the ionotropic and metabotropic glutamate receptors.
abstract: l-Glutamate is the major neurotransmitter in the central nervous system and activates both ionotropic and metabotropic receptors. Here the radiosynthesis of radiotracers developed for both types of receptors are reviewed with a highlight on the radiopharmaceuticals used or evaluated in humans. At first, radiotracers were developed for ionotropic N-methyl-d-aspartate receptors without any success to obtain radiopharmaceuticals useable for clinical or even preclinical positron emission tomography (PET) imaging purposes. Some compounds were radiolabelled and evaluated for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors without any successful results. The recent development of radiotracers for metabotropic glutamate receptors was more efficient because radiopharmaceuticals are currently evaluated or used in clinical trials to study the mGluR1, mGluR2 or mGluR5 receptors by PET. Although the majority of the radiotracers were classically labelled with carbon-11 by O- or N-[(11) C]-methylation or with fluorine-18 nucleophilic substitution of aromatic nitro or halogeno precursors using krypofix 2.2.2/potassium [(18) F]fluoride complex, some radiosyntheses were performed with recent radiolabelling reactions like the use of iodionium salt for [(18) F]-labelling.
authors.affiliation: CEA, I2BM, LDM-TEP, UMR 6301 ISTCT, GIP Cyceron, F-14074, Caen, France; CNRS, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, F-14074, Caen, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, LDM-TEP, GIP Cyceron, F-14074, Caen, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Sobrio
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes / Q000737:chemistry; D018683:Excitatory Amino Acid Agents / Q000138:chemical synthesis*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D058468:Receptors, Ionotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D018683:Excitatory Amino Acid Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D058468:Receptors, Ionotropic Glutamate; D018094:Receptors, Metabotropic Glutamate
keywords: AMPA; NMDA; PET; mGluR1; mGluR5