Development of protein-specific PET molecular imaging in neurodegenerative disorders
Project/Area Number |
19KK0212
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 52:General internal medicine and related fields
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Research Institution | Tohoku University |
Principal Investigator |
Yanai Kazuhiko 東北大学, 医学系研究科, 名誉教授 (50192787)
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Co-Investigator(Kenkyū-buntansha) |
古本 祥三 東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00375198)
原田 愛子 (石木愛子) 東北大学, 加齢医学研究所, 非常勤講師 (30778634)
岡村 信行 東北医科薬科大学, 医学部, 教授 (40361076)
原田 龍一 東北大学, 医学系研究科, 助教 (60735455)
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Project Period (FY) |
2019-10-07 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 分子イメージング / 神経変性疾患 / ミスフォールディング / グリオーシス / PET / モノアミン酸化酵素B |
Outline of Research at the Start |
健常高齢者および神経変性疾患を対象としたPET研究を実施し、[F-18]SMBT-1のバイオマーカーとしての有用性を国際共同研究で確立する。アミロイド、タウPETとアストログリオーシスPETの縦断研究により、神経変性疾患におけるミスフォールディング蛋白質とアストログリオーシスの病態形成における関係を明らかにする。これと並行して、これまでのプローブ探索で構築したβシート結合化合物を数多く含む化合物ライブラリーを利用してαシヌクレインPETプローブの探索を進めるとともに、脳内のTDP-43病変の選択的検出を可能にする新たなタンパク質PETプローブによるイメージング法の開発を国際共同研究で実施する。
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Outline of Final Research Achievements |
We have developed a novel PET tracer, [18F]SMBT-1, which is selective for monoamine oxidase B (MAO-B) highly expressed in reactive astrocytes. First-in-human study of [18F]SMBT-1 was conducted at the University of Melbourne, Australia, in an international collaborative study to clarify its safety and usefulness. The results confirmed the safety of [18F]SMBT-1 and its selectivity against MAO-B in humans. Furthermore, elevated [18F]SMBT-1 binding was observed from the cognitively normal in the presence of amyloid accumulation (Preclinical AD), indicating that astrogliosis is manifested from the early stage of the disease.
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Academic Significance and Societal Importance of the Research Achievements |
アストログリオーシスのバイオマーカーはアルツハイマー病をはじめとする神経変性疾患において病態解明や疾患修飾薬のサロゲートマーカーとして有用であると考えられ、ヒトに利用できるものが求められていた。本研究により[18F]SMBT-1がヒトにおいてMAO-Bに選択的であることが実証された。また、Preclinical ADという病初期からアストログリオーシスが顕在化していることを見出し、今後病態解明や疾患修飾薬の評価などの応用が期待される。
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Report
(5 results)
Research Products
(59 results)
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[Journal Article] In vivo [18F]THK-5351 imaging detected reactive astrogliosis in argyrophilic grain disease with comorbid pathology: A clinicopathological study2023
Author(s)
Ryota Kobayashi , Tadaho Nakamura, Fumito Naganuma, Ryuichi Harada, Daichi Morioka, Masafumi Kanoto, Shozo Furumoto, Yukitsuka Kudo, Takanobu Kabasawa, Koichi Otani, Mitsuru Futakuchi , Shinobu Kawakatsu, Nobuyuki Okamura
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Journal Title
J Neuropathol Exp Neurol .
Volume: -
Issue: 5
Pages: 427-437
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Age-related increase of monoamine oxidase B in amyloid-negative cognitively unimpaired elderly subjects.2022
Author(s)
Sakurai K, Nihashi T, Kimura Y, Iwata K, Ikenuma H, Arahata Y, Okamura N, Yanai K, Akagi A, Ito K, Kato T, Nakamura A, Group MS.
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Journal Title
Ann Nucl Med
Volume: 36(8)
Issue: 8
Pages: 777-784
DOI
Related Report
Peer Reviewed
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[Journal Article] Assessing reactive astrogliosis with 18F-SMBT-1 across the Alzheimer’s disease spectrum2022
Author(s)
Villemagne Victor L、Harada Ryuichi、Dore Vincent、Furumoto Shozo、Mulligan Rachel、Kudo Yukitsuka、Burnham Samantha、Krishnadas Natasha、Bourgeat Pierrick、Xia Ying、Laws Simon、Bozinovski Svetlana、Huang Kun、Ikonomovic Milos D、Fripp Jurgen、Yanai Kazuhiko、Okamura Nobuyuki、Rowe Christopher C
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Journal Title
Journal of Nuclear Medicine
Volume: -
Issue: 10
Pages: 1560-1569
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 18F-THK5351 PET imaging in neurodegenerative tauopathies2021
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
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Journal Title
Front Aging Neurosci
Volume: 13
Pages: 761010-761010
DOI
Related Report
Peer Reviewed / Open Access
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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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[Presentation] Physiological uptake of [18F]SMBT-1, a new astrogliosis tracer, in whole-body organs2022
Author(s)
Tashiro M, Ishioka Y, Mesfin B, Watanuki S, Hiraoka K, Harada R, Furumoto S, Okamura N, Yanai K, Watabe H
Organizer
13th Congress of the World Federation of Nuclear Medicine and Biology
Related Report
Int'l Joint Research
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[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 20222022
Author(s)
田代学, 平岡宏太良, 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
Related Report
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[Presentation] Amyloid, tau and reactive astrocytosis imaging in aging and Alzheimer’s disease2021
Author(s)
Victor L Villemagne Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Kun Huang, Kazuhiko Yanai, Christopher C Rowe, and Nobuyuki Okamura
Organizer
ADPD2021
Related Report
Int'l Joint Research
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[Presentation] Evaluation of the novel 18F-labeled PET tracer SMBT-1 for imaging astrogliosis in healthy elderly controls and in Alzheimer’s disease2020
Author(s)
Victor L Villemagne Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Kun Huang, Kazuhiko Yanai, Christopher C Rowe, and Nobuyuki Okamura
Organizer
AAIC2020
Related Report
Int'l Joint Research
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[Presentation] Development and Identification of [18F]SNFT-1 (THK-5562), a Promising Candidate for Selective Tau PET Tracer in Alzheimer’s Disease2020
Author(s)
Pradith Lerdsirisuk, Ryuichi Haradac, Yuki Shimizub, Yiqing Du, Yoichi Ishikawa, Ren Iwata, Kazuhiko Yanai, Yukitsuka Kudo, Nobuyuki Okamurab, Shozo Furumoto
Organizer
EANM2020
Related Report
Int'l Joint Research
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[Presentation] Preclinical characterization of [18F]THK-5562, a novel tau PET tracer with little off-target binding2020
Author(s)
Harada R, Lerdsirisuk P, Du Y, Ezura M, Shimizu Y, Morito T, Arai H, Yanai K,Kudo Y, Furumoto S, Okamura N
Organizer
HUMAN AMYLOID IMAGING CONFERENCE 2020(マイアミ)
Related Report
Int'l Joint Research
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