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Development of novel PET probes for imaging of metabotropic glutamate receptor subtype 2

Research Project

Project/Area Number 17H04267
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Zhang Ming-Rong  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 先進核医学基盤研究部, 部長(定常) (80443076)

Co-Investigator(Kenkyū-buntansha) 羽鳥 晶子  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 先進核医学基盤研究部, 主幹研究員(任非) (20531528)
謝 琳  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 先進核医学基盤研究部, 主任研究員(定常) (30623558)
河村 和紀  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 先進核医学基盤研究部, グループリーダー(定常) (50401766)
藤永 雅之  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 先進核医学基盤研究部, 主任研究員(定常) (70623726)
山崎 友照  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 先進核医学基盤研究部, 主任研究員(定常) (80627563)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
KeywordsPET / 分子イメージング / 代謝型グルタミン酸受容体 / mGluR2 / PETプローブ / 代謝型グルタミン酸受容体サブタイプ2 / オートラジオグラフィ / [11C]DMTN / 画像化
Outline of Final Research Achievements

Metabotropic glutamate receptor subtype 2 (mGluR2) is related to many brain diseases, such as schizophrenia. We aimed to develop useful PET probes for imaging brain mGluR2 in this project. To explore promising candidates of PET probes, we have designed 30 new compounds based on computational chemistry. By determining their binding affinity for mGluR2 and selectivity for other mGluR, iGluR, and neurotransmitters, we selected 5 promising compounds for further radiolabeling and in vivo evaluation. We labelled these compounds with carbon-11 or fluorine-18, and evaluated their potential as PET probes using in vitro autoradiography and small-animal PET. Through these studies, we have successfully discovered [11C]DMTN as a useful translational candidate for clinical use.

Academic Significance and Societal Importance of the Research Achievements

今回の研究を通じて、統合失調症等の精神神経疾患との関与が知られている代謝型グルタミン酸受容体2型サブタイプ(mGluR2)に対する有用なPETプローブ候補を開発することができた。今後、このプローブが種々の動物モデルにてさらなる有用性を証明し、また、安全性と被曝線量を評価しながら、臨床使用に対応できるPETプローブの安定製造法と分析法を確立する。将来的に臨床への橋渡し研究を進める予定である。このプローブが臨床での有用性が確認できれば、脳内mGluR2が統合失調症などとの関係を正確に評価し、様々な疾病の早期及び的確な診断につながると期待できる。また、臨床治療薬の開発にも役立つことが期待できる。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (45 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (23 results) (of which Int'l Joint Research: 17 results,  Invited: 11 results) Funded Workshop (6 results)

  • [Int'l Joint Research] Massachusetts General Hospital/University of Oklahoma/Harvard Medical School(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Nankai University/Jinan University/Nanjing Medical University(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Harvard Medical School/Massachusetts General Hospital(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Harvard Medical School/Mass General Hospital(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Radiosynthesis and evaluation of a novel monoacylglycerol lipase radiotracer: 1,1,1,3,3,3-hexafluoropropan-2-yl-3-(1-benzyl-1H-pyrazol-3-yl)azetidine-1-[11C]carboxylate2019

    • Author(s)
      Mori Wakana、Hatori Akiko、Zhang Yiding、Kurihara Yusuke、Yamasaki Tomoteru、Xie Lin、Kumata Katsushi、Hu Kuan、Fujinaga Masayuki、Zhang Ming-Rong
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 27 Issue: 16 Pages: 3568-3573

    • DOI

      10.1016/j.bmc.2019.06.037

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Design, Synthesis, and Evaluation of 18F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes2019

    • Author(s)
      Chen Zhen, Mori Wakana, Zhang Ming-Rong, Liang Steven H. et al
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 62 Issue: 19 Pages: 8866-8872

    • DOI

      10.1021/acs.jmedchem.9b00936

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 131I-IITM and 211At-AITM: Two Novel Small-Molecule Radiopharmaceuticals Targeting Oncoprotein Metabotropic Glutamate Receptor 12019

    • Author(s)
      Xie Lin、Hanyu Masayuki、Fujinaga Masayuki、Zhang Yiding、Hu Kuan、Minegishi Katsuyuki、Jiang Cuiping、Kurosawa Fuki、Morokoshi Yukie、Li Huizi Keiko、Hasegawa Sumitaka、Nagatsu Kotaro、Zhang Ming-Rong
    • Journal Title

      Journal of Nuclear Medicine

      Volume: 61 Issue: 2 Pages: 242-248

    • DOI

      10.2967/jnumed.119.230946

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a “Tail Switching” Strategy on a Piperazinyl Azetidine Skeleton2019

    • Author(s)
      Chen Zhen、Mori Wakana、Deng Xiaoyun、Cheng Ran、Ogasawara Daisuke、Zhang Genwei、Schafroth Michael A.、Dahl Kenneth、Fu Hualong、Hatori Akiko、Shao Tuo、Zhang Yiding、Yamasaki Tomoteru、Zhang Xiaofei、Rong Jian、Yu Qingzhen、Hu Kuan、Fujinaga Masayuki、Xie Lin、Kumata Katsushi、Gou Yuancheng、Chen Jingjin、Gu Shuyin
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 62 Issue: 7 Pages: 3336-3353

    • DOI

      10.1021/acs.jmedchem.8b01778

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Correction: Developing native peptide-based radiotracers for PD-L1 PET imaging and improving imaging contrast by pegylation2019

    • Author(s)
      Hu Kuan、Hanyu Masayuki、Xie Lin、Zhang Yiding、Nagatsu Kotaro、Suzuki Hisashi、Zhang Ming-Rong
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 29 Pages: 4273-4273

    • DOI

      10.1039/c9cc90113b

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and evaluation of 4-(2-fluoro-4-[11C]methoxyphenyl)-5-((2-methylpyridin-4-yl)methoxy)picolinamide for PET imaging of the metabotropic glutamate receptor 2 in the rat brain2019

    • Author(s)
      Kumata Katsushi、Hatori Akiko、Yamasaki Tomoteru、Zhang Yiding、Mori Wakana、Fujinaga Masayuki、Xie Lin、Nengaki Nobuki、Zhang Ming-Rong
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 27 Issue: 3 Pages: 483-491

    • DOI

      10.1016/j.bmc.2018.12.025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of 2-(2-(3-(4-([18F]Fluoromethoxy-d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain2018

    • Author(s)
      Mori Wakana、Yamasaki Tomoteru、Fujinaga Masayuki、Ogawa Masanao、Zhang Yiding、Hatori Akiko、Xie Lin、Kumata Katsushi、Wakizaka Hidekatsu、Kurihara Yusuke、Ohkubo Takayuki、Nengaki Nobuki、Zhang Ming-Rong
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 62 Issue: 2 Pages: 688-698

    • DOI

      10.1021/acs.jmedchem.8b01366

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of two novel [18F]fluorobenzene-containing radiotracers via spirocyclic iodonium ylides and positron emission tomography imaging of translocator protein (18 kDa) in ischemic brain2018

    • Author(s)
      Fujinaga Masayuki、Kumata Katsushi、Zhang Yiding、Hatori Akiko、Yamasaki Tomoteru、Mori Wakana、Ohkubo Takayuki、Xie Lin、Nengaki Nobuki、Zhang Ming-Rong
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 16 Issue: 37 Pages: 8325-8335

    • DOI

      10.1039/c8ob01700j

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] [18F]DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein (18?kDa)2018

    • Author(s)
      Kumata Katsushi、Zhang Yiding、Fujinaga Masayuki、Ohkubo Takayuki、Mori Wakana、Yamasaki Tomoteru、Hanyu Masayuki、Xie Lin、Hatori Akiko、Zhang Ming-Rong
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 26 Issue: 17 Pages: 4817-4822

    • DOI

      10.1016/j.bmc.2018.08.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and in vitro evaluation of three novel radiotracers for imaging of metabotropic glutamate receptor subtype 2 in rat brain2017

    • Author(s)
      Kumata Katsushi、Yamasaki Tomoteru、Hatori Akiko、Zhang Yiding、Mori Wakana、Fujinaga Masayuki、Xie Lin、Okubo Takayuki、Nengaki Nobuki、Zhang Ming-Rong
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 27 Issue: 14 Pages: 3139-3143

    • DOI

      10.1016/j.bmcl.2017.05.029

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Preliminary Studies of a Novel Negative Allosteric Modulator, 7-((2,5-Dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[11C]methoxyphenyl) quinoline-2-carboxamide, for Imaging of Metabotropic Glutamate Receptor 22017

    • Author(s)
      Zhang Xiaofei、Kumata Katsushi、Yamasaki Tomoteru、Cheng Ran、Hatori Akiko、Ma Longle、Zhang Yiding、Xie Lin、Wang Lu、Kang Hye Jin、Sheffler Douglas J.、Cosford Nicholas D. P.、Zhang Ming-Rong、Liang Steven H.
    • Journal Title

      ACS Chemical Neuroscience

      Volume: 8 Issue: 9 Pages: 1937-1948

    • DOI

      10.1021/acschemneuro.7b00098

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synthesis and evaluation of 1-(cyclopropylmethyl)-4-(4-[ 11 C]methoxyphenyl)-piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([ 11 C]CMDC) for PET imaging of metabotropic glutamate receptor 2 in the rat brain2017

    • Author(s)
      Ma Yufei、Kumata Katsushi、Yui Joji、Zhang Yiding、Yamasaki Tomoteru、Hatori Akiko、Fujinaga Masayuki、Nengaki Nobuki、Xie Lin、Wang Hui、Zhang Ming-Rong
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 25 Issue: 3 Pages: 1014-1021

    • DOI

      10.1016/j.bmc.2016.12.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] A platform of Radiopharmaceutical Development for Positron Emission Tomography Imaging and Targeted Radionuclide Therapy Studies2020

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      The International Forum on Innovative Medicine
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 代謝型グルタミン酸受容体2に選択的な新規[11C]標識PETリガンドの合成と評価2019

    • Author(s)
      熊田勝志, 山崎友照, 張一鼎, 森若菜, 藤永雅之, 羽鳥晶子, 念垣信樹, 張明栄
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Small-animal PET study: excess glutamate release upregulates mGluR1 availability2019

    • Author(s)
      山崎友照, 岡田真希, 森若菜, 張一鼎, 脇坂秀克, 小川政直, 藤永雅之, 張明栄
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Radiosynthesis and evaluation of a negative allosteric modulator for the PET imaging of metabotropic glutamate receptor 2 in rat brain2019

    • Author(s)
      Kumata K, Zhang Y, Hatori A, Yamasaki T, Kurihara Y, Nengaki N, Zhang MR
    • Organizer
      The 23nd International symposium on radiopharmaceutical science (ISRS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthesis and evaluation of a new PET ligand for imaging of monoacylglycerol lipase in brain2019

    • Author(s)
      Mori W, Kurihara Y, Hatori A, Zhang Y, Fujinaga M, Zhang MR
    • Organizer
      The 23nd International symposium on radiopharmaceutical science (ISRS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of scandium-catalyzed N-[18F]fluoroalkylation of aryl and heteroaryl amines with [18F]epifluorohydrin2019

    • Author(s)
      Fujinaga M, Ohkubo T, Kumata K, Nengaki N, Zhang MR
    • Organizer
      The 23nd International symposium on radiopharmaceutical science (ISRS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of Radiopharmaceuticals for PET Imaging and Targeted Radionuclide Therapy2019

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      The 15th Hangzhou International Molecular Imaging Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of PET Tracers for Imaging of Neuroinflammation and Dementia2019

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      The 2nd International symposium on PET Ligand Development and Molecular Imaging
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 211-At-Labeled Radiotracers: Synthesis and Preclinical Evaluation2019

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      The 14th International Conference on the Radiopharmaceutical Therapy (ICRT)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Preclinical PET imaging of inflammation in peripheral system with radioligands for translocator protein (18 kDa)2019

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      The 13th Asia Oceania of Nuclear Medicine and Biology (AOCNMB2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of PET tracers for neuroinflammation in Alzheimer’s disease2019

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      World Molecular Imaging Congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 代謝型グルタミン酸受容体2に選択的な新規11C-標識PETリガンドの合成と評価2018

    • Author(s)
      熊田勝志、山崎友照、張一鼎、森若菜、羽鳥晶子、藤永雅之、念垣信樹、張明栄
    • Organizer
      第58回日本核医学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Practical radiolabelling techniques with 18F for development of PET radiotracers for clinical use2018

    • Author(s)
      張 明栄
    • Organizer
      第58回日本核医学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] PD-L1をターゲットするPET診断及びがん免疫治療用の新規標識ペプチドの開発研究2018

    • Author(s)
      Hu Kuan, 謝 琳, 破入 正行, 張 明栄
    • Organizer
      第2回日本核医学会分科会 放射性薬品科学研究会 第18回放射性医薬品・画像診断薬研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of Radiolabeling Techniques and Clinically Useful PET Tracers for Neuroimaging2018

    • Author(s)
      張 明栄
    • Organizer
      The 1st International Symposium on PET Ligand Development and Molecular NeuroImaging & The 5th PET
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of Useful Radioprobes for Targeted Radionuclide Therapy and PET Imgaing Studies2018

    • Author(s)
      張 明栄
    • Organizer
      The 4th International Symposium on Molecular Imaging and Nanomedicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development and Application of radiotracers for Metabotropic Glutamate Receptor Subtype 1: from PET Imaging to Targeted Radionuclide Therapy2018

    • Author(s)
      張 明栄
    • Organizer
      The 3rd China-America Nuclear Medicine Academic Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 18F-FEDAC Translocator Protein PET/CT for the early detection of mitochondria dysfunction secondary to myocardial ischemia2018

    • Author(s)
      Rui Luo, Feng WANG, Ming-Rong Zhang
    • Organizer
      SNMMI 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development and radiotherapeutic effect of two novel I-131 or At-211 labelled radioprobes for melanoma with overexpressed metabotropic glutamate receptor 12018

    • Author(s)
      Masayuki Hanyu, Lin Xie, Masayuki Fujinaga, Yiding Zhang, Akiko Hatori, Yukie Morokoshi, Huizi Li, Katsuyuki Minegishi, Sumitaka Hasegawa, Kotaro Nagatsu, Ming-Rong Zhang
    • Organizer
      12th Congress of the World federation of Nuclear Medicine and Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規代謝型グルタミン酸2型受容体選択的PETリガンドの合成と評価2017

    • Author(s)
      熊田勝志, 山崎友照, 張一鼎, 羽鳥 晶子, 藤永 雅之, 念垣 信樹, 張 明栄
    • Organizer
      第57回日本核医学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of new radioprobes for PET imaging of metabotropic glutamate receptor subtype 2 in rat brain2017

    • Author(s)
      Katsushi Kumata, Tomoteru Yamasaki, Yiding Zhang, Akiko Hatori, Wakana Mori, Masayuki Fujinaga, Ming-Rong Zhang
    • Organizer
      SNMMI 2017Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of [11C]CMDC for PET imaging of metabotropic glutamate receptor 2 in the rat brain2017

    • Author(s)
      Katsushi Kumata, Yiding Zhang, Akiko Hatori, Tomoteru Yamasaki, Takayuki Ohkubo, Yusuke Kurihara, Masayuki Fujinaga, Lin Xie, Kazunori Kawamura, Ming-Rong Zhang
    • Organizer
      22nd International symposium on radiopharmaceutical science (ISRS)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of New Radiolabeling Techniques and Useful Radioprobes for Clinical Study2017

    • Author(s)
      Ming-Rong Zhang
    • Organizer
      分子イメージング厦門国際学会2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Funded Workshop] ベトナムハノイサイクロトロン10周年記念学会2019

    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] ICRT20192019

    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] SNMMI20192019

    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] ISRS20192019

    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] 2019AOCNMB2019

    • Related Report
      2019 Annual Research Report
  • [Funded Workshop] WMIC20192019

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-23  

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