title: Noninvasive quantification of metabotropic glutamate receptor type 1 with [¹¹C]ITDM: a small-animal PET study.
abstract: Because of its role in multiple central nervous system (CNS) pathways, metabotropic glutamate receptor type 1 (mGluR1) is a crucial target in the development of pharmaceuticals for CNS disorders. N-[4-[6-(isopropylamino)-pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]-methylbenzamide ([(11)C]ITDM) was recently developed as a positron emission tomography (PET) ligand for mGluR1. To devise a method for measurement of the binding potential (BPND) of [(11)C]ITDM to mGluR1, reference tissue methods aimed at replacing measurement of the arterial input function are desirable. In this study, we evaluated a noninvasive quantification method of mGluR1 with [(11)C]ITDM, demonstrating its accuracy using Huntington disease model R6/2 mice. The BPND measurements based on the Logan reference (Logan Ref) method have closely approximated that based on the arterial input method. We performed PET analysis with Logan Ref to assess its accuracy in quantifying the decline of mGluR1 expression in R6/2 mice. Significant decreases in BPND values in R6/2 mice were detected in cerebellum, thalamus, striatum, and cingulate cortex. We compared autoradiographs of R6/2 mouse brain sections with immunohistochemical images, and found a close correlation between changes in radioactive signal intensity and degree of mGluR1 expression. In conclusion, [(11)C]ITDM-PET is a promising tool for in vivo quantification of mGluR1 expression.
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.affiliation: Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.affiliation: SHI Accelerator Service Co Ltd, Tokyo, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nengaki
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001345:Autoradiography; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: D001549:Benzamides; C086055:HTT protein, human; D000071058:Huntingtin Protein; D008024:Ligands; C578808:N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N-methyl-4-(11C)methylbenzamide; D009419:Nerve Tissue Proteins; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1