Development and in vivo application of hyperpolarized molecular probes for aminopeptidase activities
| Project/Area Number |
20K15396
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 37010:Bio-related chemistry
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Saito Yutaro 東京大学, 大学院工学系研究科(工学部), 助教 (10846281)
|
|---|
| Project Period (FY) |
2020-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 超核偏極 / MRI / アミノペプチダーゼ / 分子プローブ / 超偏極分子プローブ / 動的核偏極 / アミノペプチダーゼN / 分子イメージング / 超偏極 / アミノペプチダーゼ活性 |
|---|
| Outline of Research at the Start |
アミノペプチダーゼは様々な生命現象に関与し、その活性異常は多くの疾患と相関をもつ。そのため、生体内のアミノペプチダーゼ活性をリアルタイムで観測できれば、生命現象の解明や新しい診断手法の開発につながる。これを達成するため、動的核偏極（DNP）を用いた核磁気共鳴（NMR/MRI）に着目した。NMRは生体深部の分子を観測する手法として有力であるが、格段に感度が低いという欠点がある。DNPはこの欠点を克服する方法として注目されている。本研究では、生体深部でのアミノペプチダーゼ活性検出を可能にするDNP-NMR分子プローブの開発と生体内アミノペプチダーゼ活性を解析する新たな計測技術の確立を目指す。
|
| Outline of Final Research Achievements |
Dynamic nuclear polarization (DNP) is a technique that dramatically enhances MRI sensitivity and is expected to be applied to next-generation diagnostic techniques. On the other hand, many issues remain in the development of molecular probes necessary for the application of this technology. In particular, the lack of a wide variety of molecular probes applicable in vivo and the absence of guidelines for designing new molecular probes have been major problems.
In this study, it was attempted to develop DNP-MRI molecular probes that detect the activity of aminopeptidases, a group of enzymes that are important in biological phenomena. As a result, a new DNP-MRI molecular probe was developed by precisely designing the molecule targeting aminopeptidase N (APN), which is closely related to angiogenesis, metastasis, and malignancy of cancer. The developed probe was applied to animal models and succeeded in detecting APN activity in vivo and visualizing enzyme activity in tumors.
|
| Academic Significance and Societal Importance of the Research Achievements |
動的核偏極 (DNP) 法を用いた核磁気共鳴イメージング (MRI) は、新しい早期診断法や疾患メカニズム解明につながる技術として注目されている。一方、この技術を医療や生命科学に応用するには課題が残されている。本研究成果は、その課題の一つである、分子プローブの多様性の欠乏を解決することに貢献できるものと考えられる。今後、この成果によって得られた分子設計指針を活用することでさらに新しい分子プローブが開発されることが期待される。
|
Report
(3 results)
Research Products
(16 results)
-
-
-
[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
-
Journal Title
Science advances
Volume: 8
Issue: 13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[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
-
Journal Title
DOI
Related Report
Open Access / Int'l Joint Research
-
-
-
[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
Int'l Joint Research / Invited
-
-
-
-
-
-
-
-
-
