PET imaging of astrocytes during the development of Alzheimer's disease

• Project/Area Number: 15K19787
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Osaka University
• Principal Investigator: Watabe Tadashi 大阪大学, 医学系研究科, 助教 (90648932)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: アストロサイト / PET / フルオロクエン酸 / Acetate / アルツハイマー病モデル / Alzheimer病 / PETイメージング

Outline of Final Research Achievements

Fluorocitrate (FC) is a metabolic inhibitor of tricarbonic acid (TCA) cycle specifically in astrocyte and acetate uptake is a marker of astrocytic TCA cycle activity in brain. Oxygen-15 (15O) PET is the reference standard for quantitative assessment of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2). The primary purpose of this study was to evaluate whether the inhibition of astrocytic TCA cycle metabolism by FC will affect the oxygen metabolism in the rat brain. There were no significant differences between the ipsilateral and contralateral striatum in each parameter using the 15O-gas PET. In 14C-acetate autoradiography results, there is significant inhibition in the astrocyte metabolism after FC injection in the ipsilateral striatum.Regional cerebral oxygen consumption as well as hemodynamic parameters was maintained against the inhibition of astrocytic TCA cycle metabolism in the rat brain.

Research Products

• [Journal Article] Oxygen-15 labeled CO2, O2, and CO PET in small animals: evaluation using a 3D-mode microPET scanner and impact of reconstruction algorithms. (2017)
  • Author(s): Horitsugi G, Watabe T, Kanai Y, Ikeda H, Kato H, Naka S, Ishibashi M, Matsunaga K, Isohashi K, Shimosegawa E, Hatazawa J.
  • Journal Title: EJNMMI Res Volume: 7 Issue: 1 Pages: 91-91
  • DOI: 10.1186/s13550-017-0335-7
  • Peer Reviewed / Open Access
• [Presentation] Preserved Cerebral Oxygen Metabolism against Astrocytic Dysfunction: A Combination Study of O-15 Gas PET with C-14 Acetate Autoradiography (2018)
  • Author(s): Carla Mari Macaisa; Tadashi Watabe; Yuwei Liu; Victor Romanov; Yasukazu Kanai; Genki Horitsugi; Hiroki Kato; Eku Shimosegawa; Jun Hatazawa
  • Organizer: SNMMI2018(米国核医学会）
  • Int'l Joint Research
• [Book] BIO Clinica (2017)
  • Author(s): 渡部直史
  • Total Pages: 5
  • Publisher: (株)北隆館