Development of PET probes targeting P2X7 receptor for imaging neuroinflammation

• Project/Area Number: 15K09904
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Showa 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: ¥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)
• Keywords: PET / 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.

Research Products

• [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
  • 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
• [Presentation] Development of a PET probe targeting P2X7 receptor for imaging neuroinflammation (2016)
  • 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
  • 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
• [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
  • Int'l Joint Research