Your browser doesn't support javascript.
loading
Synthesis and Evaluation of Novel Radioligands Based on 3-[5-(Pyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile for Positron Emission Tomography Imaging of Metabotropic Glutamate Receptor Subtype 5.
Shimoda, Yoko; Yamasaki, Tomoteru; Fujinaga, Masayuki; Ogawa, Masanao; Kurihara, Yusuke; Nengaki, Nobuki; Kumata, Katsushi; Yui, Joji; Hatori, Akiko; Xie, Lin; Zhang, Yiding; Kawamura, Kazunori; Zhang, Ming-Rong.
Affiliation
  • Shimoda Y; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Yamasaki T; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Fujinaga M; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Ogawa M; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Kurihara Y; SHI Accelerator Service Co. Ltd., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan.
  • Nengaki N; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Kumata K; SHI Accelerator Service Co. Ltd., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan.
  • Yui J; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Hatori A; SHI Accelerator Service Co. Ltd., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan.
  • Xie L; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Zhang Y; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Kawamura K; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • Zhang MR; Department of Radiopharmaceuticals Development, Radiological Science Research and Development Directorate, National Institutes for Quantum and Radiological Science and Technology , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
J Med Chem ; 59(8): 3980-90, 2016 04 28.
Article in En | MEDLINE | ID: mdl-27015128
ABSTRACT
We found out 3-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]benzonitrile analogues as the candidate for positron emission tomography (PET) imaging agents of metabotropic glutamate receptor subtype 5 (mGluR5). Among these compounds, 3-methyl-5-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)benzonitrile (10) exhibited high binding affinity (Ki = 9.4 nM) and moderate lipophilicity (cLogD, 2.4). Subsequently, [(11)C]10 was radiosynthesized at 25 ± 14% radiochemical yield (n = 11) via C-[(11)C]methylation of the arylstannyl precursor 15 with [(11)C]methyl iodide. In vitro autoradiography and PET assessments using [(11)C]10 showed high specific binding in the striatum and hippocampus, two brain regions enriched with mGluR5. Moreover, test-retest PET studies with [(11)C]10 indicated high reliability to quantify mGluR5 density, such as the intraclass correlation coefficient (0.90) and Pearson r (0.91) in the striatum of rat brain. We demonstrated that [(11)C]10 is a useful PET ligand for imaging and quantitative analysis of mGluR5. Furthermore, [(11)C]10 might be modified using its skeleton as a lead compound.
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyridines / Tetrazoles / Receptor, Metabotropic Glutamate 5 Limits: Animals Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2016 Document type: Article Affiliation country: Japan
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyridines / Tetrazoles / Receptor, Metabotropic Glutamate 5 Limits: Animals Language: En Journal: J Med Chem Journal subject: QUIMICA Year: 2016 Document type: Article Affiliation country: Japan