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Development of PET probes targeting P2X7 receptor for imaging neuroinflammation

Research Project

Project/Area Number 15K09904
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionShowa Pharmaceutical University

Principal Investigator

SHUKURI Miho  昭和薬科大学, 薬学部, 助教 (20525571)

Co-Investigator(Kenkyū-buntansha) 加藤 孝一  国立研究開発法人国立精神・神経医療研究センター, 脳病態統合イメージングセンター, 室長 (50382198)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsPET / ミクログリア / P2X7受容体 / P2X7 / 神経炎症 / ATP / ピログルタミン酸 / リポポリサッカライド
Outline of Final Research Achievements

The aim of the present study was the development of PET probes targeting P2X7 purinoreceptor (P2X7R) for imaging neuroinflammation.
In this study, we synthesized 11C labeled pyroglutamic acid amide derivatives (11C-PGAAs) and performed PET studies by using rats treated with intrastriatal injection of lipopolysacchalaide (LPS). The increased radioactivities of 11C-PGAAs were shown in the LPS treated hemisphere. Kinetic analysis of PET data revealed that the uptake values of 11C-PGAAs in the brain were not so high. In immunohistochemical studies, we found the activated microglia expressing increment of P2X7R in the brain regions where 11C-PGAAs showed high radioactivity. These results suggest the possibility of P2X7R as an imaging target specific to activated microglia during neuroinflammatory processes.
Although further studies to improve brain uptake are required, 11C-PGAAs showed some adequate properties for imaging P2X7R in neuroinflammation with PET.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Detection of Cyclooxygenase-1 in Activated Microglia During Amyloid Plaque Progression: PET Studies in Alzheimer's Disease Model Mice.2016

    • Author(s)
      Miho Shukuri, Aya Mawatari, Masahiro Ohno, Masaaki Suzuki, Hisashi Doi, Yasuyoshi Watanabe, Hirotaka Onoe
    • Journal Title

      Journal of Nuclear Medicine

      Volume: 57 Issue: 2 Pages: 291-296

    • DOI

      10.2967/jnumed.115.166116

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 多発性硬化症のPET診断2015

    • Author(s)
      PET journal
    • Journal Title

      PET journal

      Volume: 31 Pages: 32-34

    • Related Report
      2015 Research-status Report
  • [Presentation] Development of a PET probe targeting P2X7 receptor for imaging neuroinflammation2016

    • Author(s)
      Miho Shukuri, Kato Koichi, Kumamoto Takuya, Ihara Naoki, Hanakawa Takashi
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] P2X7受容体アンタゴニスト活性をもつPETプローブの合成研究2015

    • Author(s)
      熊本卓哉、堤田真梨、藤井愛子、片川和明、宿里充穂、伊原尚樹、加藤孝一、花川 隆
    • Organizer
      第70回記念有機合成化学協会関東支部シンポジウム
    • Place of Presentation
      長岡工業高等専門学校(新潟)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Research-status Report
  • [Presentation] Synthesis and evaluation of 11C-labeled pyroglutamic acid amide derivatives for the imaging of glial cells by PET.2015

    • Author(s)
      Koichi Kato, Miho Shukuri, Takuya Kumamoto, Naoki Ihara, Makoto Funasaka, Takashi Hanakawa
    • Organizer
      The 21st International Symposium on Radiopharmaceutical Sciences
    • Place of Presentation
      University of Missouri Research Reactor Center (Columbia, USA)
    • Year and Date
      2015-05-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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