title: Synthesis and in vitro autoradiographic evaluation of a novel high-affinity radioiodinated ligand for imaging brain cannabinoid subtype-1 receptors.
abstract: There is strong interest to study the involvement of brain cannabinoid subtype-1 (CB1) receptors in neuropsychiatric disorders with single photon emission computed tomography (SPECT) and a suitable radioligand. Here we report the synthesis of a novel high-affinity radioiodinated CB1 receptor ligand ([125I]8, [125I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate, [125I]SD7015). By autoradiography in vitro, [125I]8 showed selective binding to CB1 receptors on human brain postmortem cryosections and now merits labeling with iodine-123 for further evaluation as a SPECT radioligand in non-human primate.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Sean_Donohue@tracer.nm.jhu.edu
authors.forename: Sean R
authors.initials: SR
authors.lastname: Donohue
authors.forename: Katarina
authors.initials: K
authors.lastname: Varnäs
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Jia
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging*; D006801:Humans; D007457:Iodine Radioisotopes; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C546158:1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate; C572934:4-cyano-1-(2-iodophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; D007457:Iodine Radioisotopes; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1