title: Synthesis, in vitro and in vivo evaluation of [11C]MMTP: a potential PET ligand for mGluR1 receptors.
abstract: Synthesis, in vitro and in vivo evaluation of [O-methyl-(11)C]dimethylamino-3(4-methoxyphenyl)-3H-pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-one (1), a potential imaging agent for mGluR1 receptors using PET are described. Synthesis of the corresponding desmethyl precursor 2 was achieved by demethylation of the methoxyphenyl compound 1 in 90% yield. Methylation using [(11)C]MeOTf in presence of NaOH afforded [(11)C]1 in 30% yield (EOS) with >99% chemical and radiochemical purities and with a specific activity of 3-5Ci/micromol (n=6). The total synthesis time was 30min from EOB. The radiotracer selectively labeled mGluR1 receptors in slide-mounted sections of postmortem human brain containing cerebellum, hippocampus, prefrontal cortex and striatum as demonstrated by in vitro autoradiography using phosphor-imaging. PET studies in anesthetized baboon show that [(11)C]1 penetrates the BBB and accumulates in cerebellum, a region reported to have higher expression of mGluR1. These findings suggest [(11)C]1 is a promising PET radiotracer candidate for mGluR1.
authors.affiliation: Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Milak
authors.forename: Suham A
authors.initials: SA
authors.lastname: Kassir
authors.forename: Mikael
authors.initials: M
authors.lastname: Palner
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Savenkova
authors.forename: Pratap
authors.initials: P
authors.lastname: Mali
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.forename: J S Dileep
authors.initials: JS
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D008024:Ligands; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis*
chemical_list: C460899:5,6-dimethyl-thieno(2,3-d)pyrimidin-4(1H)-one; D002250:Carbon Radioisotopes; D008024:Ligands; D011744:Pyrimidinones; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1