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Studies on the Development of Clinical Free Radical Imaging Systme

Research Project

Project/Area Number 16H05113
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

Utsumi Hideo  静岡県立大学, 薬学部, 客員教授 (20101694)

Co-Investigator(Kenkyū-buntansha) 橋本 博  静岡県立大学, 薬学部, 教授 (40336590)
賀川 義之  静岡県立大学, 薬学部, 教授 (90397505)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
KeywordsMRI / DNP / フリーラジカル / 動的核偏極 / 常磁性物質 / イメージング / 画像診断 / DNP-MRI / ESR レドックス / 酸化ストレス / フィールドサイクル / フリーラジカル画像化 / FC-DNP-MRI / ESR / レドックス / 磁気共鳴画像 / 薬学 / 分析科学
Outline of Final Research Achievements

The dynamic nuclear polarization (DNP) MRI, a new imaging method for observing free radical species in vivo, has higher spatiotemporal resolution than that of ESR imaging, but no clinical system is developed because of the large difference in magnetic resonance conditions between nuclear and electron spins. The field-cycling is very effective to increase its sensitivity by achieving the both resonance conditions in DNP-MRI. Here we performed the basic researches about the theory of the field-cycling DNP, and obtained the fundamental results needed for the development of clinical DNP-MRI.

Academic Significance and Societal Importance of the Research Achievements

生体内レドックス代謝の画像診断装置の開発は未だ成功していない。本研究では酸化ストレスの画像診断法を開発するための基礎研究を行った。具体的には、動的核偏極を利用したMRIでレドックス代謝を可視化するためにDNPの原理に基づいて画像データを解析し、数理モデルを作成し他機関からの報告結果を含め検証した結果、高感度化に必要な基礎情報が取得できた。また、新たな「生体内常磁性物質の画像化手法技術」が開発され、新たなMRI画像化法として活用されることが期待される。

Report

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

    (39 results)

All 2019 2018 2017 2016

All Journal Article (24 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 24 results,  Open Access: 4 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Journal Article] In vivo redox imaging of dextran sodium sulfate-induced colitis in mice using Overhauser-enhanced magnetic resonance imaging2019

    • Author(s)
      Yasukawa K, Hirago A, Yamada K, Tun X, Ohkuma K, Utsumi H
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 136 Pages: 1-11

    • DOI

      10.1016/j.freeradbiomed.2019.03.025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo melanoma imaging based on dynamic nuclear polarization enhancement in melanin pigment of living mice using in vivo dynamic nuclear polarization magnetic resonance imaging2019

    • Author(s)
      Hyodo Fuminori、Naganuma Tatsuya、Eto Hinako、Murata Masaharu、Utsumi Hideo、Matsuo Masayuki
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 134 Pages: 99-105

    • DOI

      10.1016/j.freeradbiomed.2019.01.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Propolis components from stingless bees collected on South Sulawesi, Indonesia, and their xanthine oxidase inhibitory activity2019

    • Author(s)
      Miyata R, Sahlan M, Ishikawa Y, Hashimoto H, Honda S, Kumazawa S
    • Journal Title

      J. Nat. Prod.

      Volume: 82 Issue: 2 Pages: 205-210

    • DOI

      10.1021/acs.jnatprod.8b00541

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Study on the drug permeation mechanism from flurbiprofen-loaded glyceryl monooleyl ether-based lyotropic liquid crystalline nanoparticles across the skin: Synchrotron X-ray diffraction and confocal laser scanning microscopy study2019

    • Author(s)
      Uchino Tomonobu、Kato Sayaka、Hatta Ichiro、Miyazaki Yasunori、Suzuki Tomonori、Sasaki Kohta、Kagawa Yoshiyuki
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 555 Pages: 259-269

    • DOI

      10.1016/j.ijpharm.2018.11.031

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural and Thermodynamic Basis of the Enhanced Interaction between Kinesin Spindle Protein Eg5 and STLC-type Inhibitors2018

    • Author(s)
      Yokoyama Hideshi、Sawada Jun-ichi、Sato Kohei、Ogo Naohisa、Kamei Nanami、Ishikawa Yoshinobu、Hara Kodai、Asai Akira、Hashimoto Hiroshi
    • Journal Title

      ACS Omega

      Volume: 3 Issue: 9 Pages: 12284-12294

    • DOI

      10.1021/acsomega.8b00778

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enzymatic one-step ring contraction for quinolone biosynthesis2018

    • Author(s)
      Kishimoto Shinji、Hara Kodai、Hashimoto Hiroshi、Hirayama Yuichiro、Champagne Pier Alexandre、Houk Kendall N.、Tang Yi、Watanabe Kenji
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2826-2826

    • DOI

      10.1038/s41467-018-05221-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structure of proliferating cell nuclear antigen (PCNA) bound to the APIM peptide reveals universality of PCNA interaction2018

    • Author(s)
      Kodai Hara, Masayuki Uchida, Risa Tagata, Hideshi Yokoyama, Yoshinobu Ishikawa, Asami Hishiki, Hiroshi Hashimoto
    • Journal Title

      Acta Crystallogr Sect F Struct Biol Cryst Commun

      Volume: F74 Issue: 4 Pages: 214-221

    • DOI

      10.1107/s2053230x18003242

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway2018

    • Author(s)
      Masuda Yuji、Mitsuyuki Satoshi、Kanao Rie、Hishiki Asami、Hashimoto Hiroshi、Masutani Chikahide
    • Journal Title

      Nucleic Acids Research

      Volume: 46 Pages: 11340-11356

    • DOI

      10.1093/nar/gky943

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of phospholipid nanoparticles encapsulating 3-O-cetyl ascorbic acid and tocopherol acetate (TA-Cassome) for improving their skin accumulation2018

    • Author(s)
      Fushimi Tomoka、Uchino Tomonobu、Miyazaki Yasunori、Hatta Ichiro、Asano Miyuki、Fujino Hiyori、Suzuki Rie、Fujimori Shun、Kamiya Daichi、Kagawa Yoshiyuki
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 548 Issue: 1 Pages: 192-205

    • DOI

      10.1016/j.ijpharm.2018.06.030

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the molecular lipid organization in millimeter-sized stratum corneum by synchrotron X-ray diffraction2018

    • Author(s)
      Suzuki T.、Uchino T.、Hatta I.、Miyazaki Y.、Kato S.、Sasaki K.、Kagawa Y.
    • Journal Title

      Skin Research and Technology

      Volume: 24 Issue: 4 Pages: 621-629

    • DOI

      10.1111/srt.12474

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vivo Application of Proton-Electron Double-Resonance Imaging2018

    • Author(s)
      Kishimoto Shun、Krishna Murali C.、Khramtsov Valery V.、Utsumi Hideo、Lurie David J.
    • Journal Title

      Antioxidants & Redox Signaling

      Volume: 28 Issue: 15 Pages: 1345-1364

    • DOI

      10.1089/ars.2017.7341

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In Vivo Imaging of the Intra- and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging2018

    • Author(s)
      Yasukawa Keiji、Shigemi Ryota、Kanbe Tomomi、Mutsumoto Yusaku、Oda Fumiko、Ichikawa Kazuhiro、Yamada Ken-Ichi、Tun Xin、Utsumi Hideo
    • Journal Title

      Antioxidants & Redox Signaling

      Volume: in press Issue: 9 Pages: 1147-1161

    • DOI

      10.1089/ars.2017.7336

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of renal function on pharmacokinetics of antiepileptic drugs metabolized by CYP3A4 in a patient with renal impairment2018

    • Author(s)
      Yamamoto Yoshiaki、Usui Naotaka、Nishida Takuji、Mori Miho、Takahashi Yukitoshi、Imai Katsumi、Kagawa Yoshiyuki、Inoue Yushi
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 40 Issue: 1 Pages: 144-147

    • DOI

      10.1097/ftd.0000000000000461

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of neutrophil reduction using plasma paclitaxel concentration after administration in patients with uterine, ovarian, or cervical cancers in an outpatient clinic2018

    • Author(s)
      Ishikawa Motoaki、Kawai Michiyasu、Maeda Toshio、Kagawa Yoshiyuki
    • Journal Title

      Cancer Chemotherapy and Pharmacology

      Volume: 81 Issue: 2 Pages: 399-411

    • DOI

      10.1007/s00280-017-3506-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis of autoinhibition and activation of the DNA-targeting ADP-ribosyltransferase pierisin-12017

    • Author(s)
      Oda Takashi、Hirabayashi Hirokazu、Shikauchi Gen、Takamura Ryouma、Hiraga Kiyoshi、Minami Hiroshi、Hashimoto Hiroshi、Yamamoto Masafumi、Wakabayashi Keiji、Shimizu Toshiyuki、Sato Mamoru
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 37 Pages: 15445-15455

    • DOI

      10.1074/jbc.m117.776641

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanistic Insight into Weak Base-Catalyzed Generation of Carbon Monoxide from Phenyl Formate and Its Application to Catalytic Carbonylation at Room Temperature without Use of External Carbon Monoxide Gas2017

    • Author(s)
      Konishi Hideyuki、Matsubara Mika、Mori Keisuke、Tokiwa Takaki、Arulmozhiraja Sundaram、Yamamoto Yuta、Ishikawa Yoshinobu、Hashimoto Hiroshi、Shigeta Yasuteru、Tokiwa Hiroaki、Manabe Kei
    • Journal Title

      Advanced Synthesis & Catalysis

      Volume: 359 Issue: 20 Pages: 3592-3601

    • DOI

      10.1002/adsc.201700751

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP)2017

    • Author(s)
      Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno S, Tanaka K, Hashimoto H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 43 Pages: 17658-17667

    • DOI

      10.1074/jbc.m117.804237

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of molecular weight and structure on diffusion rates and mechanisms of dextran polyelectrolyte complexes2017

    • Author(s)
      Miyazaki Yasunori、Mieno Midori、Uchino Tomonobu、Kagawa Yoshiyuki
    • Journal Title

      Carbohydrate Polymers

      Volume: 162 Pages: 42-48

    • DOI

      10.1016/j.carbpol.2017.01.039

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation mechanism of the stratum corneum structure during permeation of surfactant-based rigid and elastic vesicles.2017

    • Author(s)
      Uchino T, Hatta I, Miyazaki Y, Onai T, Yamazaki T, Sugiura F, Kagawa Y.
    • Journal Title

      Int J Pharm.

      Volume: 521(1-2) Issue: 1-2 Pages: 222-231

    • DOI

      10.1016/j.ijpharm.2017.02.049

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenicity of protein aggregates of a monoclonal antibody generated by forced shaking stress with siliconized and nonsiliconized syringes in BALB/c mice2017

    • Author(s)
      Uchino Tomonobu、Miyazaki Yasunori、Yamazaki Takuto、Kagawa Yoshiyuki
    • Journal Title

      Journal of Pharmacy and Pharmacology

      Volume: 69 Issue: 10 Pages: 1341-1351

    • DOI

      10.1111/jphp.12765

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Drug Monitoring for Perampanel in Japanese Epilepsy Patients2017

    • Author(s)
      Yamamoto Yoshiaki、Usui Naotaka、Nishida Takuji、Takahashi Yukitoshi、Imai Katsumi、Kagawa Yoshiyuki、Inoue Yushi
    • Journal Title

      Therapeutic Drug Monitoring

      Volume: 39 Issue: 4 Pages: 446-449

    • DOI

      10.1097/ftd.0000000000000416

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of cytochrome P450 genotype on the plasma disposition of prochlorperazine metabolites and their relationships with clinical responses in cancer patients2017

    • Author(s)
      Tashiro Masaki、Naito Takafumi、Kagawa Yoshiyuki、Kawakami Junichi
    • Journal Title

      Annals of Clinical Biochemistry: International Journal of Laboratory Medicine

      Volume: 55 Issue: 3 Pages: 385-393

    • DOI

      10.1177/0004563217731432

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electron spin resonance studies on deuterated nitroxyl spin probes used in Overhauser-enhanced magnetic resonance imaging2017

    • Author(s)
      D. David Jebaraj, Hideo Utsumi, A. Milton Franklin Benial
    • Journal Title

      Magnetic Resonance in Chemistry

      Volume: 1 February Issue: 8 Pages: 700-705

    • DOI

      10.1002/mrc.4576

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dynamic Nuclear Polarization Studies on Deuterated Nitroxyl Spin Probes2017

    • Author(s)
      David Jebaraj D, Hideo Utsumi, Milton Franklin Benial A
    • Journal Title

      Magnetic Resonance in Chemistry

      Volume: 26 April Issue: 10 Pages: 909-916

    • DOI

      10.1002/mrc.4602

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Development and Proof of Principle for Free Radical Imaging with the Novel Field-cycling in vivo DNP-MRI2018

    • Author(s)
      Hideo Utsumi, Toshiki Masumizu, Ryoma Kobayashi, Utaroh Motosugi, Tatsuya Shimizu, Tomoko Tahira, Hidenori Kajiwara, Atsushi Iikura
    • Organizer
      ISMRM 2018(Paris, France)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 電子スピン(共鳴)と生命医科学2018

    • Author(s)
      内海英雄
    • Organizer
      第57回電子スピンサイエンス学会(札幌)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The dimerization domain of the hypertrophy-responsive transcription factor GATA4 is a therapeutic target for heart failure2018

    • Author(s)
      [1]Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
    • Organizer
      第82回日本循環器学会学術集会(大阪)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心肥大応答を司る転写因子GATA4の二量体形成・DNA結合部位の同定と結晶化2018

    • Author(s)
      [2]清水聡史、原幸大、砂川陽一、菱木麻美、宮崎雄輔、刀坂泰史、船本雅文、Nurmila Sari、清水果奈、和田啓道、長谷川浩二、橋本博、森本達也
    • Organizer
      日本薬学会第138年会(金沢)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of New Field-cycling DNP-MRI for Free Radical Imaging2017

    • Author(s)
      Hideo UTSUMI, Toshiki MASUMIZU, Ryoma KOBAYASI, Hidenori KAJIWARA, Atsushi IIKURA, Fuminori HYODO, Tomoko TAHIRA
    • Organizer
      EPR2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development and Clinical Trial of Novel Field-cycling DNP-MRI for Free Radical Imaging2017

    • Author(s)
      Hideo UTSUMI, Toshiki MASUMIZU, Ryoma KOBAYASHI, Utaroh Motosugi, Tatsuya Shimizu, Fuminori Hyodo, Tomoko Tahira, Hidenori KAJIWARA, Atsushi IIKURA
    • Organizer
      SfRBM
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規フリーラジカルイメージング装置の開発と健常人介入試験2017

    • Author(s)
      内海英雄, 本杉宇太郎, 清水辰哉, 田平知子
    • Organizer
      日本磁気共鳴医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 臨床応用を指向したフリーラジカルイメージング・DNP-MRI装置の開発2017

    • Author(s)
      内海英雄, 増水章季, 小林竜馬, 梶原秀則, 飯倉淳, 兵藤文紀, 田平知子
    • Organizer
      日本磁気共鳴医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 臨床用DNP-MRIの開発とフリーラジカルの可視化2017

    • Author(s)
      内海英雄, 増水章季, 小林竜馬, 梶原秀則, 飯倉淳, 兵藤文紀, 田平知子
    • Organizer
      SEST2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 臨床応用を指向したフリーラジカルイメージング・DNP-MRI装置の開発2017

    • Author(s)
      内海英雄, 増水章季, 小林竜馬, 梶原秀則, 飯倉淳, 兵藤文紀, 田平知子
    • Organizer
      酸化ストレス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Crystallographic structure of Mad2L2-CAMP complex, a regulator of kinetochore-microtubule attachment2017

    • Author(s)
      Kodai Hara, Shota Taharazako, Asami Hishiki, Yoshinobu Ishikawa, Shin-ichiro Kanno, Kozo Tanaka, Hiroshi Hashimoto
    • Organizer
      SMC proteins 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CYCLOPENASE, HEMOCYANIN-LIKE ENZYME CONVERTING 6,7-BICYCLO RING OF CYCLOPENIN TO FORM 6,6-QUINOLONE CORE OF VIRIDICATIN-TYPE FUNGAL ALKALOID2017

    • Author(s)
      Shinji Kishimoto, Yuta Tsunematsu, Kodai Hara, Hiroshi Hashimoto, Kenji Watanabe
    • Organizer
      IUMS 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 磁石回転による主磁場制御型MRIのT1強調効果2016

    • Author(s)
      小林 竜馬、内海 英雄
    • Organizer
      NMR討論会
    • Place of Presentation
      広島国際会議場(広島県広島市)
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] T1強調撮像のための磁石回転型Field cycle MRIの開発2016

    • Author(s)
      小林 竜馬、内海 英雄
    • Organizer
      応用物理学会
    • Place of Presentation
      朱鷺メッセ(新潟)
    • Year and Date
      2016-09-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 磁石回転型Field Cycle MRIにおけるEddy Currentの効果と補正2016

    • Author(s)
      小林 竜馬、内海 英雄
    • Organizer
      日本磁気共鳴医学会
    • Place of Presentation
      大宮ソニックシティ(埼玉県大宮)
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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