• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Visualization of monoacylglycerol lipase in ischemia rat brain using [11C]SAR127303 and development of new PET probes.

Research Project

Project/Area Number 17K10461
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HATORI Akiko  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)

Co-Investigator(Kenkyū-buntansha) 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)
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)
張 明栄  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)
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 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsモノアシルグリセロールリパーゼ / MAGL / ポジトロン エミッション トモグラフィ / PET / PETプローブ / ポジトロン エミッション トモグラフィー / 画像化
Outline of Final Research Achievements

PET imaging of [11C]SAR127303 and immunohistochemical staining using ischemia rat brains revealed that brain radioactivity uptake and monoacylglycerol lipase (MAGL) expression in ischemia part decreased on the degree of ischemia damage. [11C]SAR127303, a PET probe for MAGL, has considerable promise for the evaluation of brain damage.
We also developed 11C and 18F labeled new PET probes for MAGL based on [11C]SAR127303 as the lead compound in order to improve the in vivo PET probe. Candidate probes were evaluated using animals for brain permeability, binding specificity, and kinetic studies. The irreversible MAGL probes demonstrated high in vivo binding specificity in the brain, while the reversible probes showed limited brain uptake and high binding specificity to MAGL in the peripheral tissues.

Academic Significance and Societal Importance of the Research Achievements

本研究では、MAGLのPETプローブを使用し、動物モデルの脳に存在するMAGLを画像化し定量化することにより、脳の疾患におけるMAGL活性の変化と疾患に伴う推移を明らかにすることができた。新しい治療薬が脳などの対象器官におけるMAGLの占有率を測定することにより、種々の疾患治療に新たな治療指針を提供することができると考えられる。将来の展望として、MAGL-PETを様々な病態の理解、治療薬の至適容量の設定、薬剤の有効性証明及び薬効の予測が行える新しいイメージングバイオマーカーとしての有用性を確立できると期待している。

Report

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

    (13 results)

All 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] Harvard Medical School(米国)

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

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Harvard Medical School(米国)

    • Related Report
      2017 Research-status Report
  • [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 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [ 11 C]SAR1273032018

    • Author(s)
      Yamasaki Tomoteru、Mori Wakana、Zhang Yiding、Hatori Akiko、Fujinaga Masayuki、Wakizaka Hidekatsu、Kurihara Yusuke、Wang Lu、Nengaki Nobuki、Ohya Tomoyuki、Liang Steven H.、Zhang Ming-Rong
    • Journal Title

      NeuroImage

      Volume: 176 Pages: 313-320

    • DOI

      10.1016/j.neuroimage.2018.05.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] In Vitro and in Vivo Evaluation of 11C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies2018

    • Author(s)
      Ran Cheng, Wakana Mori, Longle Ma, Mireille Alhouayek, Akiko Hatori, Yiding Zhang, Daisuke Ogasawara, Gengyang Yuan, Zhen Chen, Xiaofei Zhang, Hang Shi, Tomoteru Yamasaki, Lin Xie, Katsushi Kumata, Masayuki Fujinaga, Yuji Nagai, Takafumi Minamimoto, Mona Svensson, Lu Wang, Yunfei Du, Mary Jo Ondrechen, Neil Vasdev
    • Journal Title

      J. Med. Chem.

      Volume: 61 Issue: 6 Pages: 2278-2291

    • DOI

      10.1021/acs.jmedchem.7b01400

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [11C]SAR1273032018

    • Author(s)
      Tomoteru Yamasaki, Wakana Mori, Yiding Zhang, Akiko Hatori, Masayuki Fujinaga, Hidekatsu Wakizaka, Yusuke Kurihara, Lu Wang, Nobuki Nengaki, Tomoyuki Ohya, Steven H Liang, Ming-Rong Zhang
    • Journal Title

      NeuroImage

      Volume: 印刷中

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Visualization of MAGL in ischemia rat brain using PET probe 11C-SAR1273032019

    • Author(s)
      Akiko Hatori, Yiding Zhang, Wakana Mori, Yusuke Kurihara, Hidekatsu Wakisaka, Ming-Rong Zhang
    • Organizer
      Brain & Brain PET 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Monoacylglycerol lipaseのPETプローブ[18F]PF06795071の評価2019

    • Author(s)
      羽鳥 晶子、森 若菜、張 一鼎、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] [11C]で標識したMAGLに選択的な新規PETリガンドの合成及び動物評価2019

    • Author(s)
      森 若菜, 栗原 雄祐, 羽鳥 晶子, 張 一鼎, 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] 脳虚血モデルラットを用いたPETプローブ[11C]SAR1による脳内MAGLの画像化2018

    • Author(s)
      羽鳥 晶子、張 一鼎、森 若菜、栗原 雄祐、脇坂 秀克、張 明栄
    • Organizer
      日本核医学会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-02-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi