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Development of novel theranostics probes with EPR imaging

Research Project

Project/Area Number 16K10291
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionHealth Sciences University of Hokkaido (2018)
Sapporo Medical University (2016-2017)

Principal Investigator

EMOTO Miho  北海道医療大学, 医療技術学部, 講師 (10578735)

Co-Investigator(Kenkyū-buntansha) 藤井 博匡  札幌医科大学, 医療人育成センター, 教授 (70209013)
Research Collaborator SATO Shingo  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsEPRイメージング / Theranostics / 抗酸化 / 抗炎症作用 / ナイトロオキサイド / 抗炎症薬 / 炎症モデルマウス / ROS / 酸化ストレス
Outline of Final Research Achievements

The word ‘theranostic’ was coined in 2002 to describe a compound that exhibits both therapeutic and diagnostic capabilities. Since then, numerous nanoparticle-based theranostics have been created that can be used for hyperthermia or radiation therapy, for example, and/or for the delivery of chemotherapeutic drugs and diagnostic imaging agents. Theranostic probes provide both therapeutic and diagnostic imaging capabilities in one molecule and show significant promise for use in magnetic resonance imaging (MRI)examinations. The present study describes for the first time the synthesis and utility of nitroxide-based contrast agents exhibiting a non steroidal anti-inflammatory drug effect.

Academic Significance and Societal Importance of the Research Achievements

本研究成果によるセラノスティクスの為のプローブを開発・活用することで、個々の病状の観察と、その人にとって最もふさわしい治療を一体化して行うことを目的とした、医療における新しい流れつくる足がかりとなる。この研究により、脳内炎症モデル動物のROS生成状態や分布状況が時系列で解析可能であり、さらに抗炎症作用効果が脳内ラジカル濃度の変化として現れる事が期待される。このようなハイブリッド薬剤の効果を脳内のラジカル量やラジカル分布として計測、画像化する試みは世界初であり、成功すれば医学・薬学界に大きく貢献できるものと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (23 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Non-invasive mapping of glutathione levels in mouse brains by in vivo electron paramagnetic resonance (EPR) imaging: Applied to a kindling mouse model2019

    • Author(s)
      Emoto Miho C.、Sato-Akaba Hideo、Matsuoka Yuta、Yamada Ken-ichi、Fujii Hirotada G.
    • Journal Title

      Neuroscience Letters

      Volume: 690 Pages: 6-10

    • DOI

      10.1016/j.neulet.2018.10.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain Redox Imaging Using In Vivo Electron Paramagnetic Resonance Imaging and Nitroxide Imaging Probes2019

    • Author(s)
      Fujii Hirotada、Emoto Miho、Sato-Akaba Hideo
    • Journal Title

      Magnetochemistry

      Volume: 5 Issue: 1 Pages: 11-11

    • DOI

      10.3390/magnetochemistry5010011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Mitochondrial Oxidative Stress in the Brain of a Transgenic Mouse Model of Alzheimer's Disease by in vitro Electron Paramagnetic Resonance Spectroscopy.2019

    • Author(s)
      Manabe T, Matsumura A, Yokokawa K, Saito T, Fujikura M, Iwahara N, Matsushita T, Suzuki S, Hisahara S, Kawamata J, Suzuki H, Emoto MC, Fujii HG, Shimohama S.
    • Journal Title

      Journal of Alzheimer's disease

      Volume: 67 Issue: 3 Pages: 1079-1087

    • DOI

      10.3233/jad-180985

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Evaluation as a Blood–Brain Barrier-Permeable Probe of 7-<i>N</i>-(PROXYL-3-yl-methyl)theophylline2018

    • Author(s)
      Emoto Miho C.、Sasaki Kota、Maeda Koya、Fujii Hirotada G.、Sato Shingo
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 66 Issue: 9 Pages: 887-891

    • DOI

      10.1248/cpb.c18-00333

    • NAID

      130007479637

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2018-09-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging2017

    • Author(s)
      Miho C. Emoto, Yuta Matsuoka, Ken-ichi Yamada, Hideo Sato-Akaba, Hirotada G. Fujii
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 485 Issue: 4 Pages: 802-806

    • DOI

      10.1016/j.bbrc.2017.02.134

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Design and testing of a 750MHz CW-EPR digital console for small animal imaging.2017

    • Author(s)
      Sato-Akaba H, Emoto MC, Hirata H, Fujii HG
    • Journal Title

      J Magn Reson.

      Volume: 284 Pages: 48-58

    • DOI

      10.1016/j.jmr.2017.09.008

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of nitroxide-based theranostic compounds that act both as anti-inflammatory drugs and brain redox imaging probes in MRI2016

    • Author(s)
      Emoto MC, Sato S, Fujii HG
    • Journal Title

      Magnetic Resonance in Chemistry

      Volume: 54 Issue: 9 Pages: 705-711

    • DOI

      10.1002/mrc.4431

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel blood-brain-barrier-permeable spin probe for in vivo electron paramagnetic resonance imaging2016

    • Author(s)
      X. Wang, M. Emoto, Y. Miyake, K. Itto, S. Xu, H. Fujii, H. Hirata, H. Arimoto,
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 20 Pages: 4947-4949

    • DOI

      10.1016/j.bmcl.2016.09.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In Vivo Brain Redox Status in Diethylmaleate-Treated Mice Using EPR Imaging.2016

    • Author(s)
      Hirotada G Fujii, Miho C Emoto, Yuta Matsuoka, Ken-ichi Yamada
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 100 Pages: S161-S161

    • DOI

      10.1016/j.freeradbiomed.2016.10.421

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Non-invasive mapping of glutathione levels in mouse brains by electron paramagnetic resonance (EPR) imaging.2018

    • Author(s)
      Hirotada Fujii, Miho Emoto, Yuta Matsuoka, Ken-ichi Yamada, Hideo Sato-Akaba.
    • Organizer
      JOINT ANNUAL MEETING ISMRM-ESMRMB 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EPRイメージング負を用いたマウス脳内酸化ストレス状態の加齢による影響の可視化2018

    • Author(s)
      Miho Emoto, Hideo Akaba-Sato, Hirotada Fujii
    • Organizer
      第46回日本磁気共鳴医学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] EPRイメージング法による脳内グルタチオンのマッピング2018

    • Author(s)
      Hirotada Fujii, Miho Emoto, Yuta Matsuoka, Ken-ichi Yamada, Hideo Sato-Akaba
    • Organizer
      第46回日本磁気共鳴医学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] EPRイメージング法によるグルタチオンマッピング:神経疾患動物への応用を目指して2018

    • Author(s)
      藤井博匡、江本美穂、赤羽英夫、松岡悠太、山田健一
    • Organizer
      第57回電子スピンサイエンス学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Non-invasive mapping of glutathione levels in mouse brains by electron paramagnetic resonance (EPR) imaging.2018

    • Author(s)
      Hirotada Fujii, Miho Emoto, Yuta Matsuoka, Ken-ichi Yamada, Hideo Sato-Akaba.
    • Organizer
      JOINT ANNUAL MEETING ISMRM-ESMRMB
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Brain redox imaging using blood-brain-barrier nitroxides by digital EPR imaging system2017

    • Author(s)
      M.C. Emoto, Hideo Sato-Akaba, H.G. Fujii
    • Organizer
      第25回国際磁気共鳴医学会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular imaging of glutathione in mouse brain 脳内グルタチオンの分子イメージング2017

    • Author(s)
      Hirotada Fujii, Miho Emoto, Yuta Matsuoka, Ken-ichi Yamada, Hideo Sato-Akaba
    • Organizer
      第45回日本磁気共鳴医学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨髄慣用系幹細胞によるアルツハイマー病治療における脳内酸化ストレス動態の検討2017

    • Author(s)
      横川和樹、岩原直敏、江本美穂、久原真、齋藤太郎、藤倉舞、眞部建郎、鈴木紘美、松下隆司、松村晃寛、鈴木秀一郎、川又純、藤井博匡、下濱俊
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] n Vivo Brain Redox Status in Diethylmaleate-Treated Mice Using EPR Imaging2016

    • Author(s)
      Hirotada G Fujii, Miho C Emoto, Yuta Matsuoka, Ken-ichi Yamada
    • Organizer
      SfRBM's 23rd Annual Meeting
    • Place of Presentation
      サンフランシスコ(USA)
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウス脳内REDOXイメージング用Theranosticsプローブの開発2016

    • Author(s)
      藤井博匡、江本美穂、佐藤慎吾
    • Organizer
      第44回日本磁気共鳴医学会大会
    • Place of Presentation
      大宮ソニックシティ(埼玉県さいたま市)
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Bain Redox imaging using nitroxide-based theranostic Probes in septic mice2016

    • Author(s)
      FUJII G Hirotada, EMOTO C Miho, SATO Shingo
    • Organizer
      第17回International Conference on Oxidative Stress Reduction, Redox Homeostasis and Antioxidants
    • Place of Presentation
      パリ(フランス)
    • Year and Date
      2016-06-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Does Tempol enter the brain with an unpaired electron?2016

    • Author(s)
      M.C. Emoto, Hideo Sato-Akaba, H.G. Fujii
    • Organizer
      第24回国際磁気共鳴医学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-05-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of nitroxide-based theranostics probe for brain research by MRI2016

    • Author(s)
      M.C. Emoto, S Sato, H.G. Fujii
    • Organizer
      第24回国際磁気共鳴医学会
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-05-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 電子スピン共鳴装置2017

    • Inventor(s)
      赤羽英夫、藤井博匡、江本美穂
    • Industrial Property Rights Holder
      赤羽英夫、藤井博匡、江本美穂
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-050576
    • Filing Date
      2017-03-15
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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