Improved Visualization and Specific Binding for Metabotropic Glutamate Receptor Subtype 1 (mGluR1) Using [11C]ITMM with Ultra-High Specific Activity in Small-Animal PET |
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Authors: | Tomoteru Yamasaki Masayuki Fujinaga Joji Yui Hidekatsu Wakizaka Tomoyuki Ohya Nobuki Nengaki Masanao Ogawa Yoko Ikoma Akiko Hatori Lin Xie Kazunori Kawamura Ming-Rong Zhang |
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Institution: | Molucular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.; Rutgers University, UNITED STATES, |
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Abstract: | Metabotropic glutamate receptor subtype 1 (mGluR1) is a crucial target in the development of new medications to treat central nervous system (CNS) disorders. Recently, we developed N-4-6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C]methoxy-N-methyl-benzamide (11C]ITMM) as a useful positron emission tomography (PET) probe for mGluR1 in clinical studies. Here, we aimed to improve visualization and threshold of specific binding for mGluR1 using 11C]ITMM with ultra-high specific activity (SA) of > 3,500 GBq/μmol in rat brains. A two-tissue compartment model indicated large differences between the two SAs in the constants k3 and k4, representing binding ability for mGluR1, while constants K
1 and k2 showed no differences. The total distribution volume (VT) values of conventional and ultra-high SA were 9.1 and 11.2 in the thalamus, 7.7 and 9.7 in the striatum, and 6.4 and 8.5 mL/cm3 in the substantia nigra, respectively. The specific binding of 11C]ITMM with ultra-high SA was significantly higher than the conventional SA, especially in the basal ganglia. Parametric PET images scaled with VT of the ultra-high SA clearly identified regional differences in the rat brain. In conclusion, PET studies using 11C]ITMM with ultra-high SA could sufficiently improve visualization and specific binding for mGluR1, which could help further understanding for mGluR1 functions in CNS disorders. |
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