Development of a novel diagnostic imaging marker in acute cerebral ischemia

• Project/Area Number: 15K15464
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Mizuma Hiroshi 国立研究開発法人理化学研究所, ライフサイエンス技術基盤研究センター, 研究員 (00382200)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脳梗塞 / 画像診断 / PET / ラット

Outline of Final Research Achievements

Fluoroacetate (FACE) has been known to be incorporated into astrocyte and acts as a metabolic toxin by blocking the tricarboxylic acid cycle. The aim of this study was to determine whether 18F-labelled FACE ([18F]FACE) is useful for a novel diagnostic imaging marker in acute cerebral ischemia. Cerebral ischemia model rats were made by occluding the right middle cerebral artery (MCA) for 60 min followed by subsequent reperfusion. [18F]FACE-PET scan was conducted under isoflurane anesthesia. [18F]FACE was highly accumulated in the ischemic region during MCA occlusion with low cerebral flow, in which no [18F]FACE metabolite was observed. Histological analyses revealed that [18F]FACE accumulation was not associated with appearance of reactive astrocyte and breakdown of blood brain barrier. These finding indicate that ischemia causes changes in astrocyte energy metabolism and also alter FACE transportation, in other words [18F]FACE can be a promising PET probe in acute cerebral ischemia.

Research Products

• [Presentation] 2-[18F]fluoroacetate as an imaging biomarker for cerebral ischemia (2016)
  • Author(s): Mizuma H, Kagawa S, Ohno M, Matsumoto Y, Kakumoto K, Higashi T, Nishii R, Onoe H
  • Organizer: SNMMI2016, Annual Meeting of Society of Nuclear Medicine and Molecular Imaging
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] 蒸留法によるBenzyl [18F]Fluoroacetateの合成基礎検討 (2015)
  • Author(s): 加川信也，水間広，西井龍一，東達也，山内浩，大野正裕，高橋和弘，尾上浩隆，川井恵一
  • Organizer: 第55回日本核医学会学術総会
  • Place of Presentation: ハイアットリージェンシー東京（東京都・新宿区）
  • Year and Date: 2015-11-05
• [Presentation] Accumulation of [18F]FACE in cerebral ischemia (2015)
  • Author(s): Mizuma H, Kagawa S, Ohno M, Kakumoto K, Matsumoto Y, Higashi T, Nishii R & Onoe H
  • Organizer: World Molecular Imaging Congress 2015
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] 臨床使用に向けた Benzyl[18F]Fluoroacetate の合成及び製剤化の検討 (2015)
  • Author(s): 加川信也，水間広，矢倉栄幸，西井龍一，東達也，山内浩，立石裕行，大野正裕，高橋和弘，尾上浩隆，川井恵一
  • Organizer: 第10回日本分子イメージング学会総会・学術集会
  • Place of Presentation: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2015-05-20
• [Presentation] フルオロ酢酸のラット脳における[18F]FDG 取込みに対する影響 (2015)
  • Author(s): 水間広，加川信也，大野正裕，角元恭子，松本佳乃，東達也，西井龍一，尾上浩隆
  • Organizer: 第10回日本分子イメージング学会総会・学術集会
  • Place of Presentation: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2015-05-20
• [Presentation] 早期脳虚血におけるフルオロ酢酸PET (2015)
  • Author(s): 西井龍一，水間広，加川信也，大野正裕，合瀬恭幸，林拓也，高橋和弘，尾上浩隆
  • Organizer: 第74回日本医学放射線学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2015-04-16