Tau-Gliosis Interaction in Tauopathies using Pathological Imaging

• Project/Area Number: 18K15357
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Tohoku Medical and Pharmaceutical University (2022); Tohoku University (2018-2021)
• Principal Investigator: Harada Aiko 東北医科薬科大学, 医学部, 助教 (30778634)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アルツハイマー病 / タウ / グリオーシス / PET / 神経炎症 / アミロイド / MAO-B / アルツハイマー

Outline of Final Research Achievements

An optimized MAO-B-selective PET tracer 18F-SMBT1, in which the tau binding of 18F-THK5351 was removed, was developed and the gliosis evaluation was switched to 18F-SMBT1. The tau PET tracer 18F-SNFT1 was not available for clinical trials during the period of this study. Therefore, 18F-SMBT1 and 11C-PiB PET were performed in this study. In healthy subjects, 18F-SMBT1 accumulated in the thalamus, striatum, and brainstem regions, and in those with mild cognitive impairment or Alzheimer's disease, in the frontal, temporal, parietal, and cingulate gyri. A follow-up study was conducted in one healthy subject, and 18F-SMBT1 SUVR was almost invariant in the whole brain.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病を初めとした認知症性疾患は未だに根本治療がなく、主に原因タンパク質をターゲットとした治療薬開発が盛んである。本研究により脳内の炎症と原因タンパク質との相互関係が明らかになれば、現在開発中の治療法をさらに補強する新規治療法の開発につながる可能性がある。本研究により脳内の加齢性変化が可視化され、また認知症性疾患では加齢性変化に加え異常な神経炎症が生じていることが明らかとなった。後続研究により経時的変化および原因タンパク質との相互関係が明らかになれば、治療ターゲットが変わる可能性もあり、大きく期待される。

Research Products

• [Int'l Joint Research] Melbourne University(オーストラリア)
• [Int'l Joint Research] Austin Health, Melbourne(オーストラリア)
• [Journal Article] 18F-THK5351 PET imaging in neurodegenerative tauopathies (2021)
  • Author(s): Ezura M, Kikuchi A, Okamura N, Ishiki A, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Ishiyama S, Nakamura T, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
  • Journal Title: Front Aging Neurosci Volume: 13 Pages: 761010-761010
  • DOI: 10.3389/fnagi.2021.761010
  • Peer Reviewed / Open Access
• [Journal Article] 18F-SMBT-1: A Selective and Reversible PET Tracer for Monoamine Oxidase-B Imaging (2020)
  • Author(s): Harada Ryuichi、Hayakawa Yoshimi、Ezura Michinori、Lerdsirisuk Pradith、Du Yiqing、Ishikawa Yoichi、Iwata Ren、Shidahara Miho、Ishiki Aiko、Kikuchi Akio、Arai Hiroyuki、Kudo Yukitsuka、Yanai Kazuhiko、Furumoto Shozo、Okamura Nobuyuki
  • Journal Title: Journal of Nuclear Medicine Volume: 62 Issue: 2 Pages: 253-258
  • DOI: 10.2967/jnumed.120.244400
  • Peer Reviewed
• [Presentation] 認知症疾患の層別化における[18F]SMBT-1の有用性の検討プロジェクトの経過報告2022 (2022)
  • Author(s): 田代学, 平岡宏太良, 冨田尚希, 石木愛子, 小林良太, 四月朔日聖一, メスフィン・ベリフ, 武田和子, 草場美津江, 菊池昭夫, 渡部浩司, 麦倉俊司, 古川勝敏, 加藤隆司, 石井賢二, 川勝忍, 原田龍一, 古本祥三, 岡村信行.
  • Organizer: 第41回日本認知症学会学術集会
• [Presentation] 神経炎症イメージングのための新規PET薬剤[18F]SMBT-1の動態解析（Work in Progress） (2022)
  • Author(s): 平岡宏太良、メスフィン・ベリフ、石岡有生、四月朔日聖一、石川洋一、船木善仁、稲村瑛仁、原田龍一、石木愛子、古本祥三、岡村信行、渡部浩司、田代学.
  • Organizer: 第42回日本医学放射線学会北日本地方会／日本核医学会北日本地方会
• [Presentation] Development of 18F-SNFT1, a novel tau PET tracer with little off-target binding (2020)
  • Author(s): Aiko Ishiki, Ryuichi Harada, Pradith Lerdsirisuk, Yiqing Du, Michinori Ezura, Kazuhiko Yanai, Shozo Furumoto, Yukitsuka Kudo, Hiroyuki Arai, Nobuyuki Okamura
  • Organizer: Alzheimer Association International conference
  • Int'l Joint Research
• [Presentation] Assessing Aβ, tau, and reactive astrocytosis in aging and AD. 14th Human Amyloid Imaging (2020)
  • Author(s): Victor Villemagne
  • Organizer: 14th Human Amyloid Imaging
  • Int'l Joint Research
• [Presentation] Preclinical characterization of [18F]THK-5562, a novel tau PET tracer with little off-target binding. (2020)
  • Author(s): Ryuichi Harada
  • Organizer: 14th Human Amyloid Imaging
  • Int'l Joint Research
• [Presentation] Discovery of [18F]SMBT-1: a novel selective MAO-B PET tracer for imaging astrogliosis. (2019)
  • Author(s): Ryuichi Harada
  • Organizer: 13th Human Amyloid Imaging
  • Int'l Joint Research
• [Presentation] DEVELOPMENT OF A NOVEL 18F-LABELED PET TRACER FOR IMAGING ASTROGLIOSIS (2019)
  • Author(s): Nobuyuki Okamura
  • Organizer: Alzheimer's Association International Conference 2019
  • Int'l Joint Research
• [Remarks] Tau PET: The Field Expands Rapidly
  • URL: https://www.alzforum.org/news/conference-coverage/tau-pet-field-expands-rapidly