title: Evaluation of [3H]LY341495 for labeling group II metabotropic glutamate receptors in vivo.
abstract: New glutamatergic drugs are being developed as potential therapies for neurodegenerative disorders, anxiety disorders, and psychoses. The development of effective mGluR radiotracers would provide essential tools with which to probe these sites in living humans, providing critical information about certain disease processes involving the glutamaterigic system and its regulation in humans. As a first step towards this goal, the tritiated form of the high affinity group II metabotropic glutamate receptor (mGluR) antagonist LY341495 [K(D) (mGluR(2)) = 1.67 +/- 0.20 nM, K(D) (mGluR(3)) = 0.75 +/- 0.43 nM] was evaluated to determine its potential to label mGluRs in vivo. Dissection analysis of the regional brain distribution over time of [(3)H]LY341495 in male rats revealed low brain uptake and no significant demonstrable saturable binding of this tracer. A group II mGluR tracer possessing higher affinity than [(3)H]LY341495 and an absence of carboxylic acid groups is likely required for in vivo PET imaging purposes.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY 10032, USA. rnw7@columbia.edu
authors.forename: Rikki N
authors.initials: RN
authors.lastname: Waterhouse
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schmidt
authors.forename: Abida
authors.initials: A
authors.lastname: Sultana
authors.forename: Darryle D
authors.initials: DD
authors.lastname: Schoepp
authors.forename: William J
authors.initials: WJ
authors.lastname: Wheeler
authors.forename: P David
authors.initials: PD
authors.lastname: Mozley
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
mesh_terms: D000596:Amino Acids / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011869:Radioligand Assay / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013696:Temperature; D014018:Tissue Distribution; D014316:Tritium / Q000097:blood / Q000493:pharmacokinetics; D014966:Xanthenes / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000596:Amino Acids; C114624:LY 341495; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; D014316:Tritium