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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 ( BP  ND ) 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 BP  ND  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 BP  ND  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.

Noninvasive Quantification of Metabotropic Glutamate Receptor Type 1 with [11C]ITDM: a Small-Animal PET Study

Noninvasive Quantification of Metabotropic Glutamate Receptor Type 1 with [¹¹C]ITDM: a Small-Animal PET Study