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A model study for personalized cancer medicine by the novel chemoradiotherapy guided on the state-of-the-art spin resonance imaging

Research Project

Project/Area Number 17K01363
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

Takakusagi Yoichi  国立研究開発法人量子科学技術研究開発機構, 量子生命科学領域, 主任研究員(任常) (60439916)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords電子スピン共鳴 / 酸素 / 低酸素標的薬 / 動的核偏極 / ピルビン酸 / イメージング / 放射線治療 / 個別化医療 / 放射線増感剤 / 超偏極
Outline of Final Research Achievements

In this study, a model experiment was conducted to improve the treatment outcome of cancer by using the in vivo imaging technique for the application of new chemo-radiotherapy. Prior to the treatment, physiological characteristics of tumors, such as hypoxia formation or enhanced aerobic glycolysis, which are associated with treatment resistance, were non-invasively visualized using spin resonance imaging techniques. Based on the imaging data with partial oxygen pressure (pO2) or metabolic properties, appropriate therapeutic options (type of radiosensitizer, radiation dose, and their treatment schedule) were determined to maximize the therapeutic effect. As support, imaging during the treatment as well as biopsy tests was conducted in parallel to determine the optimal treatment protocol.

Academic Significance and Societal Importance of the Research Achievements

本課題の in vivo 画像技術は、癌の悪性化や治療耐性に関わる低酸素領域の形成や糖代謝の亢進を、生体を傷つけることなく超高感度かつダイナミックに調べることが可能な最先端の技術である。作用メカニズムの異なる臨床開発中の新しい放射線増感剤を組み合わせた個別化医療のモデル実験によりそれらの応用方法や有用性を具体的に示し、当該分野の先駆的な研究成果として後続の研究を牽引する。また、本成果を基盤とした臨床開発の進展により、その精度を格段に向上させた新たながん診断治療技術として、がんの治療成績の向上へと貢献する可能性が期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (50 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (36 results) (of which Int'l Joint Research: 9 results,  Invited: 18 results) Remarks (1 results)

  • [Int'l Joint Research] NCI/NIH/NINDS/NIH/Threshold Pharmaceuticals(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] NCI/NIH/NINDS/NIH/Threshold Pharmaceuticals(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] NCI/NIH/NINDS/NIH/Threshold Pharmaceuticals(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Radiation Biology Branch, NCI/NIH/Threshold Pharmaceuticals(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Phage display technology for target determination of small-molecule therapeutics: an update2020

    • Author(s)
      Yoichi Takakusagi, Kaori Takakusagi, Kengo Sakaguchi, Fumio Sugawara
    • Journal Title

      Expert Opin Drug Discov

      Volume: 15 Issue: 10 Pages: 1199-1211

    • DOI

      10.1080/17460441.2020.1790523

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions2020

    • Author(s)
      Yoichi Takakusagi
    • Journal Title

      J Vis Exp

      Volume: 166 Issue: 166

    • DOI

      10.3791/61873

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 超偏極-核磁気共鳴代謝イメージングと生命科学・医療への応用展開2020

    • Author(s)
      高草木洋一
    • Journal Title

      月刊OPTRONICS 8 月号

      Volume: 39 Pages: 79-83

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 含硫糖脂質 SQAG の放射線増感作用メカニズムの解明2019

    • Author(s)
      高草木洋一、Sarwat Naz、高草木香織、坂口謙吾、菅原二三男、James B Mitchell、Murali C Krishna
    • Journal Title

      第 61 回天然有機化合物討論会講演要旨集

      Volume: 09 Pages: 511-516

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Multimodal Molecular Imaging Study Evaluates Pharmacological Alteration of the Tumor Microenvironment to Improve Radiation Response2018

    • Author(s)
      Takakusagi, Y. Naz, S. Takakusagi, K. Ishima, M. Murata, H. Ohta, K. Miura, M. Sugawara, F. Sakaguchi, K. Kishimoto, S. Munasinghe, J. P. Mitchell, J. B. Krishna, M. C.
    • Journal Title

      Cancer Res

      Volume: 78 Issue: 24 Pages: 6828-6837

    • DOI

      10.1158/0008-5472.can-18-1654

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Using the QCM Biosensor-Based T7 Phage Display Combined with Bioinformatics Analysis for Target Identification of Bioactive Small Molecule2018

    • Author(s)
      Takakusagi, Y. Takakusagi, K. Sugawara, F. Sakaguchi, K.
    • Journal Title

      Methods Mol Biol

      Volume: 1795 Pages: 159-172

    • DOI

      10.1007/978-1-4939-7874-8_14

    • ISBN
      9781493978731, 9781493978748
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolic and Physiologic Imaging Biomarkers of the Tumor Microenvironment Predict Treatment Outcome with Radiation or a Hypoxia-Activated Prodrug in Mice2018

    • Author(s)
      Matsumoto, S. Kishimoto, S. Saito, K. Takakusagi, Y. Munasinghe, J. P. Devasahayam, N. Hart, C. P. Gillies, R. J. Mitchell, J. B. Krishna, M. C.
    • Journal Title

      Cancer Res

      Volume: 78 Issue: 14 Pages: 3783-3792

    • DOI

      10.1158/0008-5472.can-18-0491

    • NAID

      120006651800

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging of prostate cancer in vivo predicts efficacy of targeting the Warburg effect2018

    • Author(s)
      Scroggins B, Matsuo M, White A, Saito K, Munasinghe JP, Sourbier C, Yamamoto K, Diaz V, Ichikawa K, Mitchell JB, Cherukuri MK, Citrin DE
    • Journal Title

      Clinical Cancer Research

      Volume: 印刷中 Issue: 13 Pages: 3137-3148

    • DOI

      10.1158/1078-0432.ccr-17-1957

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro and In Vivo Studies2018

    • Author(s)
      Yoichi Takakusagi, Shun Kishimoto, Sarwat Naz, Shingo Matsumoto, Keita Saito, Charles P. Hart, James B. Mitchell, Murali C. Krishna
    • Journal Title

      Antioxid Redox Signal

      Volume: 28 Issue: 2 Pages: 131-140

    • DOI

      10.1089/ars.2017.7106

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 動的核偏極-核磁気共鳴法 ~分子代謝と生命現象の谷間をつなぐ新たな架け橋~2021

    • Author(s)
      高草木洋一
    • Organizer
      バイオインダストリー奨励賞受賞者企画講演会 ~生命現象の根本的解明を目指す量子生命科学について~
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 超偏極-核磁気共鳴代謝イメージング: 分子プローブの開発と応用計測にみる課題と展望2020

    • Author(s)
      高草木洋一
    • Organizer
      量子生命科学会第 2 回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] QST 量子生命科学領域/量子超偏極 MRI グループの紹介2020

    • Author(s)
      高草木洋一
    • Organizer
      第 48 回日本磁気共鳴医学会大会 超偏極による他核MRSIの高感度計測スタディーグループ
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 動的核偏極がもたらす新しいサイエンスと医療応用を求めて2020

    • Author(s)
      高草木洋一
    • Organizer
      大阪大学 CiNET セミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Novel Real-time Hyperpolarized 13C Metabolic Tracer Probes gamma-Glutamyl Transferase Activities in vivo Human Tumor Xenografts2020

    • Author(s)
      Kazutoshi Yamamoto , Tomohiro Seki , Nobu Oshima , Marino Itoda , Yohei Kondo , Yutaro Saito , Yoichi Takakusagi , Shun Kishimoto , Jeffery Brender , Ronja Malinowski , Jan Henrik Ardenkjaer-Larsen , Hiroshi Nonaka , Murali Krishna , Shinsuke Sando
    • Organizer
      61st ENC
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel Real-time Hyperpolarized 13C Metabolic Tracer Probes γ-Glutamyl Transferase Activities in vivo Tumor Xenografts2020

    • Author(s)
      Tomohiro Seki , Kazutoshi Yamamoto , Nobu Oshima , Marino Itoda , Yohei Kondo , Yutaro Saito , Yoichi Takakusagi , Shun Kishimoto , Jeffery Brender , Ronja Malinowski , Jan Henrik Ardenkjaer-Larsen , Hiroshi Nonaka , Murali C Krishna , Shinsuke Sando
    • Organizer
      ISMRM
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体内ペプチダーゼ活性検出のための実用的量子超偏極 MRI 分子プローブ開発2020

    • Author(s)
      齋藤雄太朗 , 谷田部浩行 , 田村伊織 , 近藤洋平 , 石田諒 , 関智宏 , 江口晃弘 , 高草木洋一 , 山本和俊 , Murali C. Krishna , 山東信介
    • Organizer
      量子生命科学会第 2 回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生体内アミノペプチダーゼの活性を検出する超偏極分子プローブの開発2020

    • Author(s)
      谷田部浩行 , 田村伊織 , 近藤洋平 , 高草木洋一 , 石田諒 , 山本和俊 , Murali C Krishna , 齋藤雄太朗 , 山東信介
    • Organizer
      第 10 回 CSJ 化学フェスタ 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生体内アミノペプチダーゼN活性を検出する超偏極分子プローブの開発2020

    • Author(s)
      齋藤雄太朗 , 谷田部浩行 , 田村伊織 , 近藤洋平 , 石田諒 , 関智宏 , 江口晃弘 , 高草木洋一 , 山本和俊 , Murali C Krishna , 山東信介
    • Organizer
      第 14 回バイオ関連化学シンポジウム 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 生体内ペプチダーゼの活性を検出する超偏極分子プローブの開発2020

    • Author(s)
      谷田部浩行 , 齋藤雄太朗 , 石田諒 , 田村伊織 , 近藤洋平 , 高草木洋一 , 山本和俊 , Murali C Krishna , 山東信介
    • Organizer
      日本化学会第100 回春季年会 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 量子超偏極-核磁気共鳴分子プローブによるアミノペプチダーゼ N 及びアミノペプチダーゼ A 活性の同時検出2020

    • Author(s)
      谷田部浩行 , 田村伊織 , 近藤洋平 , 高草木洋一 , 石田諒 , 山本和俊 , Murali C. Krishna , 齋藤雄太朗 , 山東信介
    • Organizer
      量子生命科学会第 2 回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A multimodal molecular imaging study of tumor microenvironment to reveal the mechanism of tumor radiosensitization elicited by a natural sulfoglycolipid2019

    • Author(s)
      Yoichi Takakusagi, Shingo Matsumoto, Masayuki Matsuo, Kaori Takakusagi, Keita Saito, Shun Kishimoto, Masahiko Miura, Toshiyasu Miyazaki, Fumio Sugawara, Kengo Sakaguchi, James B Mitchell, Murali C Krishna
    • Organizer
      第 14 回日本分子イメージング学会総会・学術集会、日本分子イメージング学会
    • Related Report
      2019 Research-status Report
  • [Presentation] マルチモダル分子イメージングによる腫瘍内微小環境の多角的評価と天然由来含硫糖脂質の誘発する放射線増感作用メカニズムの解明2019

    • Author(s)
      高草木洋一、松元慎吾、松尾政之、高草木香織、齋藤圭太、岸本俊、三浦雅彦、宮崎年恭、菅原二三男、坂口謙吾、James B Mitchell、Murali C Krishna
    • Organizer
      第 14 回日本分子イメージング学会総会・学術集会、日本分子イメージング学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 超偏極 13C MRI 代謝イメージングによる抗癌治療効果の予測2019

    • Author(s)
      松元慎吾、齋藤圭太、高草木洋一、Murali C Krishna
    • Organizer
      第 14 回日本分子イメージング学会総会・学術集会、日本分子イメージング学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 生体内 β-ガラクトシダーゼ活性検出に向けた高感度-核磁気共鳴分子プローブの検討2019

    • Author(s)
      近藤洋平、坂本大地、野中洋、高草木洋一、山本和俊、Murali C Krishna、青木伊知男、山東信介
    • Organizer
      第 14 回日本分子イメージング学会総会・学術集会、日本分子イメージング学会
    • Related Report
      2019 Research-status Report
  • [Presentation] MR マイクロイメージングと Gd-デンドロン修飾ナノリポソーム造影剤を用いた 3D 微小血管系およびナノ粒子分布の腫瘍内評価2019

    • Author(s)
      新田展大、高草木洋一、國領大介、柴田さやか、冨田章裕、東達也、青木伊知男、原田雅史
    • Organizer
      第 14 回日本分子イメージング学会総会・学術集会、日本分子イメージング学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 含硫糖脂質 SQAG の放射線増感作用メカニズムの解明2019

    • Author(s)
      高草木洋一、Sarwat Naz、高草木香織、坂口謙吾、菅原二三男、James B Mitchell、Murali C Krishna
    • Organizer
      第 61 回天然有機化合物討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] スピン共鳴画像技術の基礎と応用2019

    • Author(s)
      高草木洋一
    • Organizer
      長崎国際大学薬学部 薬品物理化学特別セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Hyperpolarized-NMR/MRI in Japan2019

    • Author(s)
      Yoichi Takakusagi
    • Organizer
      Technical University of Denmark, HYPERMAG Center, lab seminar
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Dissolution-DNP の最先端研究拠点 DTU HYPERMAG Center2019

    • Author(s)
      高草木洋一
    • Organizer
      第 47 回日本磁気共鳴医学会大会 超偏極による他核 MRSI の高感度計測
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 低分子有機化合物の魅力 ~探す、創る、使う~2019

    • Author(s)
      高草木洋一
    • Organizer
      第 1 回量子生命科学会 若手の会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 放射線研究における超偏極-核磁気共鳴分光法とイメージングの応用2019

    • Author(s)
      高草木洋一
    • Organizer
      日本放射線影響学会第 62 回大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 先端量子技術: 超偏極の最先端と実用化への期待2018

    • Author(s)
      高草木洋一
    • Organizer
      第 3 回 MRI アライアンス国際シンポジウム
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 超偏ー[1-13C]ピルビン酸 MRS によるがんスフェロイドの初期エネルギー代謝変化の非侵襲計測2018

    • Author(s)
      高草木洋一、高草木香織、井上香織、市川和洋
    • Organizer
      第 46 回 日本磁気共鳴医学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Use of hyperpolarized magnetic resonance spectroscopy (HP-MRS) in cell and tissue engineering2018

    • Author(s)
      Yoichi Takakusagi, Kaori Takakusagi, Kaori Inoue, Kazuhiro Ichikawa
    • Organizer
      5th Tissue Engineering and Regenerative Medicine International Society World Congress (TERMIS)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hyperpolarized [1-13C]pyruvate MRS reveals increased aerobic glycolysis in the ultra-early phase of PSA-negative prostate carcinogenesis2018

    • Author(s)
      Yoichi Takakusagi, Kaori Takakusagi, Kaori Inoue, Kazuhiro Ichikawa
    • Organizer
      HYP18―An International Conference on Nuclear Hyperpolarization
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] バイオセンシングにより解き明かす生体内分子ダイナミクス2018

    • Author(s)
      高草木洋一
    • Organizer
      第 12 回 QCM 研究会セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] スピン共鳴画像解析と新規化学放射線療法によるがんのセラノスティクス2018

    • Author(s)
      高草木洋一
    • Organizer
      第 12 回 QCM 研究会セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] QCM-T7 ファージディスプレイ法によるがん血管新生阻害剤の標的タンパク質および結合部位の同定2018

    • Author(s)
      高草木香織、高草木洋一
    • Organizer
      第 12 回 QCM 研究会セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Hyperpolarized [1-13C]pyruvate MRS reveals early-phase transition of energy metabolism in multicellular spheroid tumors2018

    • Author(s)
      Yoichi Takakusagi, Kaori Takakusagi, Kaori Inoue, Kazuhiro Ichikawa
    • Organizer
      International Society for Magnetic Resonance in Medicine (ISMRM) 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Monitoring effect of rapamaycin on pyruvate metabolism in SCC tumor using hyperpolarized 13C-MRI2018

    • Author(s)
      Keita Saito, Shingo Matsumoto, Yoichi Takakusagi, Masayuki Matsuo, Hellmut Merkle, James B. Mitchell, Murali C. Krishna
    • Organizer
      International Society for Magnetic Resonance in Medicine (ISMRM) 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 最先端量子イメージングによる膵臓がん個別化医療のモデル研究2018

    • Author(s)
      松元慎吾、高草木洋一、齋藤圭太、岸本俊、Mitchell J.B.、Hart C.P.、Gillies R.J.、Krishna M.C.
    • Organizer
      第 2 回量子生命科学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 画像診断と治療のコンビネーション: セラノスティクスとコンパニオン診断2018

    • Author(s)
      高草木洋一
    • Organizer
      第 115 回日本医学物理学会学術大会 早朝教育講演
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 動的核偏極-核磁気共鳴分子プローブの創製と応用計測2017

    • Author(s)
      高草木洋一
    • Organizer
      次世代 MRI・造影剤 キックオフ国際シンポジウム
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 超偏極-核磁気共鳴分子プローブの創製と応用計測 ~次世代画像診断技術としての実用化を目指して~2017

    • Author(s)
      高草木洋一
    • Organizer
      第 45 回磁気共鳴医学会大会 シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Accessories and Techniques that Maximize MRI as a Quantum Technology2017

    • Author(s)
      Yoichi Takakusagi
    • Organizer
      A Workshop on Drawing Biological Information through Quantum Spin Systems (NCI/NIH Bldg10)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 国立研究開発法人量子科学技術研究開発機構 量子生命科学研究所 量子超偏極 MRI グループ

    • URL

      https://www.qst.go.jp/site/iqls/44735.html

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2022-02-21  

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