Development of PET probes for visualization of neurodegenerative process
| Project/Area Number |
18K15538
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 放射性医薬品 / PET / アストロサイト / タウ / PETプローブ |
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| Outline of Final Research Achievements |
18F-THK-5351 PET have limited biomarker for tau pathology in Alzheimer’s disease because of off-target binding to monoamine oxidase-B, which is dominantly expressed in astrocytes. Selective imaging techniques to trace tau burden and astrogliosis selectively are required to elucidate neuronal circuit breakdown mechanisms in the humans. The aim of this study was to develop novel and selective PET probes for imaging tau pathology and MAO-B, respectively through compound optimization from 18F-THK-5351. We synthesized more than 200 compounds and screened against tau aggregates and MAO-B. Finally, we successfully discovered novel selective PET probes for imaging tau pathology and MAO-B that possess preferable pharmacokinetics.
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| Academic Significance and Societal Importance of the Research Achievements |
タウ病変を非侵襲的に画像化することができればアルツハイマー病の診断や治療薬のサロゲートマーカーへの利用が期待できる。研究代表者らはこれまでにタウ病変を画像化する目的でPETプローブ18F-THK-5351を開発したが、オフターゲットの問題が発覚し、改良を余儀なくされた。本研究で改良した18F-SNFT-1はタウ病変に選択的であり、タウを標的とした治療薬のサロゲートマーカーとして有望であると考えられる。また、本研究で開発したMAO-B選択的なPETプローブ18F-SMBT-1によりアストログリオーシスを選択的に描出することが可能となり、治療薬が神経炎症に与える影響の効果判定への応用が期待される。
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Longitudinal changes in 18F-THK5351 PET in corticobasal syndrome2019
Author(s)
Ezura M, Kikuchi A, Ishiki A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
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Journal Title
Eur J Neurol
Volume: 26
Issue: 9
Pages: 1205-1211
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Newly-Developed Positron Emission Mammography (PEM) Device for the Detection of Small Breast Cancer2018
Author(s)
Yanai A, Itoh M, Hirakawa H, Yanai K, Tashiro M, Harada R, Yoshikawa A, Yamamoto S, Ohuchi N, Ishida T.
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Journal Title
The Tohoku Journal of Experimental Medicine
Volume: 245
Issue: 1
Pages: 13-19
DOI
NAID
ISSN
0040-8727, 1349-3329
Related Report
Peer Reviewed / Open Access
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[Presentation] Preclicanil characterization of [18F]THK-5562, a novel tau PET tracer with little off-target binding2020
Author(s)
Ryuichi Harada, Pradith Lerdisirisuk, Yiqing Du, Michinori Ezura, Yuki Shimizu, Takahiro Morito, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo, Shozo Furumoto, Nobuyuki Okamura
Organizer
Human Amyloid Imging 2020
Related Report
Int'l Joint Research
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[Presentation] Assessing Abeta, tau, and reactive astrocytosis in aging and AD2020
Author(s)
Victor Villemagne, Ryuichi Harada, Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Natasha KrisKun Huang, Kazuhiko Yanai, Christopher C Rowe, Nobuyuki Okamura
Organizer
Human Amyloid Imging 2020
Related Report
Int'l Joint Research
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