| Project/Area Number |
17K09813
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Ishii Kenji 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (10231135)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Alzheimer病 / タウイメージング / PET / [C-11]PBB3 / [F-18]THK5351 / 病理 / 画像病理相関 |
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| Outline of Final Research Achievements |
We conduced head-to-head comparison study of two tau PET tracers, [C-11]PBB3 and [F-18]THK5351, in the accumulation to human brain. Seventeen cases were examined and autopsy was obtained in three cases. THK5351 appeared to have binding to monoamineoxidase-B (MAO-B), and the selectivity to tau was limited. However, the binding capability to MAO-B make it possible to visualize neurodegenerative/neuroinflammatory lesions with astrogliosis as hot spot with very high sensitivity. MAO-B imaging may be useful to evaluate the localization of neurodegenerative lesions.
PBB3 seems to have cross accumulation to amyloid beta and sensitivity to bind tau lesion is relatively low, however, it appeared to visualize not only 3R/4R tau lesions, but also 4R tau lesion in PSP and CBD. Therefore, PBB3 has potential advantage to visualize tau accumulation in the amyloid negative (non-Alzheimer) neurodegenerative diseases such as 4R tauopathies.
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| Academic Significance and Societal Importance of the Research Achievements |
タウPET診断薬は、何れも非特異的集積（off-target binding）を有し、感度も十分とは言えない。また、Alzheimer病のタウ描出に優れたトレーサーが必ずしも他のタウオパチーの診断に適しているわけではない。
本研究は、タウPET診断薬にはそれぞれ固有の集積の特徴と意義があり、目的によって使い分ける必要があることを明らかにした。
また、MAO-Bイメージングによるアストロサイト活性化診断は、変性病態の局在をホットスポットとして評価できる優れた診断技術であり、今後病態評価への活用が期待される。
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