Sensitive Molecular Imaging Based on Hyperpolarization Molecular Technique
| Project/Area Number |
19H00919
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 37:Biomolecular chemistry and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SANDO SHINSUKE 東京大学, 大学院工学系研究科(工学部), 教授 (20346084)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000)
Fiscal Year 2021: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2020: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2019: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
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| Keywords | 分子イメージング / 核偏極 / 分子プローブ・分子造影剤 / 代謝・生体微小環境 / MRI |
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| Outline of Research at the Start |
体の中の分子の構造変化や化学反応などの分子の動的な“活動”（すなわち、代謝や生体微小環境変化）を計測することができる超高感度―核磁気共鳴分子技術の確立を目指す。核磁気共鳴計測の最大の問題点である“低感度”の向上を実現する核偏極―核磁気共鳴技術に着目、生体応用可能な分子プローブ・分子センサーを開発し、今まで調べられなかった生体内における分子の動的な活動の計測を実現する。分子レベルでの生命現象の解明や疾患早期診断につながる研究を進めていく。
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| Outline of Final Research Achievements |
Nuclear spin relaxation T1 is mainly governed by five relaxation factors: DD, SC, SR, CSA, and Others. By minimizing these relaxation factors from the molecular structure, it is possible to develop a molecular scaffold that realizes a long T1, i.e., long-lived nuclear spin polarization.
In this research, I focused on (1) 15N, which has a small gyro-magnetic ratio and is expected to achieve long-lived nuclear polarization, and (2) 13C, which is expected to achieve high-sensitivity measurement, to develop hyperpolarized molecular probes, based on experimental and theoretical approaches. A series of hyperpolarized molecular probes with 15N and 13C as hyperpolarized nuclei were developed. Some of these probes have been demonstrated to work in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
体の中の分子の活動の理解は、分子の集合体としての生命の根源的な仕組みの理解に繋がる。また、生体内で起こる化学物質変換としての代謝や生体微小環境の変化から引き起こされる疾病の原因解明、早期診断、さらには、その治療法開発に大きな進歩をもたらすことができる。その実現に向け、本研究課題では、体の中の分子の構造を直接計測することができる核磁気共鳴技術に着目し、その最大の問題点である“感度”の向上を実現する分子プローブレパートリーの拡張を目指した。実験的解釈と理論的解析に基づいて核偏極―核磁気共鳴分子プローブ設計指針の確立に取り組み、13C核や15N核を中心とした長寿命核偏極分子プローブの開発を実現した。
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Report
(5 results)
Research Products
(30 results)
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[Journal Article] Structure-based relaxation analysis reveals C-terminal [1-13C]glycine-d2 in peptides has long spin-lattice relaxation time that is applicable to in vivo hyperpolarized magnetic resonance studies2022
Author(s)
Yohei Kondo, Yutaro Saito, Tomohiro Seki, Yoichi Takakusagi, Jumpei Morimoto, Hiroshi Nonaka, Koichiro Miyanishi, Wataru Mizukami, Makoto Negoro, Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Masayuki Matsuo, Natarajan Raju, Rolf Swenson, Murali C. Krishna, Kazutoshi Yamamoto, Shinsuke Sando
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Journal Title
DOI
Related Report
Open Access / Int'l Joint Research
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[Journal Article] Structure-guided design enables development of a hyperpolarized molecular probe for the detection of aminopeptidase N activity in vivo2022
Author(s)
Yutaro Saito, Hiroyuki Yatabe, Iori Tamura, Yohei Kondo, Ryo Ishida, Tomohiro Seki, Keita Hiraga, Akihiro Eguchi, Yoichi Takakusagi, Keisuke Saito, Nobu Oshima, Hiroshi Ishikita, Kazutoshi Yamamoto, Murali C. Krishna, Shinsuke Sando
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Journal Title
Science advances
Volume: 8
Issue: 13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Development of hyperpolarized molecular probes for in vivo detection of peptidase activities2021
Author(s)
Yutaro Saito, Hiroyuki Yatabe, Iori Tamura, Ryo Ishida, Yohei Kondo, Tomohiro Seki, Akihiro Eguchi, Yoichi Takakusagi, Kazutoshi Yamamoto, Murali C. Krishna, Shinsuke Sando
Organizer
Pacifichem 2021
Related Report
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[Presentation] Development of a Hyperpolarized Molecular Probe for in vivo Detection of Aminopeptidase N Activity2019
Author(s)
Yutaro Saito, Yohei Kondo, Ryo Ishida, Tomohiro Seki, Iori Tamura, Hiroyuki Yatabe, Yoichi Takakusagi, Kazutoshi Yamamoto, Hiroshi Nonaka, Murali C. Krishna, Shinsuke Sando
Organizer
日本化学会第100春季年会
Related Report
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