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Originally Synthesized Oxy-Redox Sensitive Contrast Substances for in vivo Mapping of Tissue Redox and Oxidant Status in Cancer Using High Field MRI

Research Project

Project/Area Number 21611011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical Physics/Radiological Technology
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

ZHELEV Zhivko  独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (60511532)

Co-Investigator(Renkei-kenkyūsha) AOKI Ichio  独立行政法人放射線医学総合研究所, 分子イメージング研究センター, チームリーダー (10319519)
BAKALOVA Rumiana  独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (30469936)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
KeywordsMRI / Cancer / Nitroxyl / ニトロキシルラジカル / 酸化還元 / ESR / マウス / 酸化還元状態 / 大腸がん / 高磁場MRI / フリーラジカル / 電子スピン共鳴 / nitroxide / neuroblastoma
Research Abstract

I investigated the redox potential, hydrophobicity and T_1 relaxivity of 15 redox sensitive nitroxide probes, using voltametry, EPR spectroscopy and T_1 weighted MRI. The probes were classified in three groups, depending on their hydrophobicity-hydrophilic, slightly hydrophobic and strongly hydrophobic. In each group the probes were classified in two subgroups, depending on its resistance to reduction-rapidly reducing and slowly reducing. Four probes were selected for application in imaging of tissue redox activity in experimental animals using MRI. I established that there is difference in tissue redox activity between early and moderate/terminal stage of cancer development, as well as between tumor core and tumor periphery.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (27 results)

All 2011 2010 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (14 results) Remarks (1 results)

  • [Journal Article] Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics2011

    • Author(s)
      Bakalova R, Zhelev Z, Kokuryo D, Spasov L, Aoki I, Saga T
    • Journal Title

      Int J Nanomedicine

      Volume: 6 Pages: 1719-32

    • Related Report
      2011 Final Research Report
  • [Journal Article] Carbamoyl-PROXYL-enhanced MRI detects very small disruptions in brain vascular permeability induced by dietary cholesterol2011

    • Author(s)
      Tomizawa A, Ishii I, Zhelev Z, Aoki I, Shibata S, Kitada M, Bakalova R
    • Journal Title

      Biochim Biophys Acta

      Volume: 1810(12) Pages: 1309-16

    • Related Report
      2011 Final Research Report
  • [Journal Article] Nitroxide derivatives for imaging of hypercholesterolemia-induced kidney dysfunction and assessing the effectiveness of antilipidemic drugs2011

    • Author(s)
      Tomizawa A, Hadjidekov G, Ishii I, Bakalova R, Zhelev Z, Aoki I, Saga T, Kitada M
    • Journal Title

      Mol Pharm

      Volume: 8(5) Pages: 1962-9

    • Related Report
      2011 Final Research Report
  • [Journal Article] Chemical nature and structure of organic coating of quantum dots is crucial for their application in imaging diagnostics2011

    • Author(s)
      Bakalova R., Zhelev Z., Kokuryou D., Spasov L., Aoki I., Saga T.
    • Journal Title

      Int J Nanomedicine

      Volume: 6:1719 Pages: 1719-1732

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carbamoyl-PROXYL-enhanced MRI detects very small disruptions in brain vascular permeability induced by dietary cholesterol2011

    • Author(s)
      Tomizawa A., Ishii I., Zhelev Z., Aoki I., Shibata S., Kitada M., Bakaliva R.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1810(12)1309-16 Pages: 1309-1316

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nitroxide derivatives for imaging of hypercholesterolemia-induced kidney dysfunction and assessing the effectiveness of antilipidemic drugs2011

    • Author(s)
      Tomizawa A., Hadjidekov G., Ishii II., Bakalova R., Zheliv Z., Aoki I., Saga T., Kitada M.
    • Journal Title

      Mol Pharm

      Volume: 3;8(5):1962-9 Pages: 1962-1969

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical nature and structure of organic coating of quantum dots iscrucial for their application in imaging diagnostic in vivo2011

    • Author(s)
      Bakalova R., Z.Zhelev, D.Kokuryo, L.Spasov, I.Aoki, S.Saga
    • Journal Title

      International Journal of Nanornedicine

      Volume: in Press(Peer-review)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imaging of cancer by redox-mediated mechanism : a radical diagnostic approach2010

    • Author(s)
      Zhelev Z, Bakalova R, Aoki I, Gadjeva V, Kanno I
    • Journal Title

      Mol Biosyst

      Volume: 6(12) Pages: 2386-8

    • Related Report
      2011 Final Research Report
  • [Journal Article] Imaging of cabcer bt redix mediated mechanism : a redical diagnostic approach2010

    • Author(s)
      Zhivko Zhelev.Rumiana Bakalova-Zheleva, Ichio Aoki, Gadjeva Veselina, Iwao Kanno
    • Journal Title

      Molecular BioSystems

      Volume: 6(12) Pages: 2386-2388

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EPR signal reduction kinetic of several nitroxyl derivatives in blood in vitro and in vivo2009

    • Author(s)
      Zhelev Z, Matsumoto K, Gadjeva V, Bakalova R, Aoki I, Zheleva A, Anzai K
    • Journal Title

      Gen Physiol Biophys

      Volume: 28(4) Pages: 356-62

    • Related Report
      2011 Final Research Report
  • [Journal Article] Nitroxyl radicals for labeling of conventional therapeutics and noninvasive magnetic resonance imaging of their permeability for blood-brain barrier : relationship between structure, blood clearance, and MRI signal dynamic in the brain2009

    • Author(s)
      Zhelev Z, Bakalova R, Aoki I, Matsumoto K, Gadjeva V, Anzai K, Kanno I
    • Journal Title

      Mol Pharm

      Volume: 6(2) Pages: 504-12

    • Related Report
      2011 Final Research Report
  • [Journal Article] EPR signal reduction kinetics of several nitroxyl derivatives in blood in vitro and in vivo2009

    • Author(s)
      Zhelev Z., Matsumoto K., Gadjeva V., Aoki I., et al.
    • Journal Title

      General Physiology and Biophysics 28

      Pages: 356-362

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] -Nitroxide probes as redox sensors for imaging of cancer in vivo2011

    • Author(s)
      Bakalova, R., Z. Zhelev, S. Shibata, L. Spasov, and I. Aoki
    • Organizer
      International Conference on Biomaterials Science
    • Place of Presentation
      Tsukuba, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] -Magnetic resonance imaging of redox activity in the brain of normal and cancer-bearing mammalians : a radical diagnostic approach2011

    • Author(s)
      Zhelev, Z., R. Bakalova, S. Shibata, L. Spasov, and I. Aoki
    • Organizer
      XXVth International Symposium on Ccerebral Blood Flow, Metabolism and Function
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2011 Final Research Report
  • [Presentation] -Magnetic resonance imaging of very small disruptions of blood vessel permeability in hypercholesterolemia mice using nitroxide probes2010

    • Author(s)
      Bakalova, R., I. Ishii, Z. Zhelev, S. Shibata, I. Aoki, and M. Kitada
    • Organizer
      Annual Conference of the Japanese Society for Molecular Imaging
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Magnetic Resonance Imaging of Cancer Based on Tissue Redlox Activity2010

    • Author(s)
      Zhivko Zhelev Rumiana Bakalova-Zheleva, Ichio Aoki, Sayaka Shibata, Gadjeva Veselina, Iwao Kanno
    • Organizer
      The Society for Molecular Imaging
    • Place of Presentation
      日本 京都市
    • Related Report
      2010 Annual Research Report
  • [Presentation] Magnetic Resonance Imaging of Very Small Disruptions of Blood Vessel Permeability in Hypercholesterolemia Mice Using Nitroxide Probes2010

    • Author(s)
      Rumiana Bakalova-Zheleva, Itsuko Ishii, Zhivko Zhelev, Ichio Aoki, Iwao Kanno, et.al
    • Organizer
      日本分子イメージング学会
    • Place of Presentation
      日本 大津市
    • Related Report
      2010 Annual Research Report
  • [Presentation] Diagnostic Potential of Nitroxide Radicals in Cancer Using Magnetic Resonance Imaging Tomography2010

    • Author(s)
      Zhivko Zhelev, Rumiana Bakalova-Zheleva, Ichio Aoki, Gadjeva Veselina, Iwao Kanno
    • Organizer
      日本分子イメージング学会
    • Place of Presentation
      日本 大津市(口頭発表)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Diagnostic Potential of Nitroxide Radicals in Cancer Using Magnetic Resonance Imaging Tomography2010

    • Author(s)
      Zhivko Zhelev, Rumiana Bakalova-Zheleva, Ichio Aoki, Gadjeva Veselina, Iwao Kanno
    • Organizer
      日本分子イメージング学会
    • Place of Presentation
      日本 大津市(ポスター発表)
    • Related Report
      2010 Annual Research Report
  • [Presentation] -Nitroxide radicals in brain imaging using T1 weighted MRI2009

    • Author(s)
      Zhelev Z., Bakalova R., Matsumoto K., Aoki I., Gadjeva V., Anzai K., Kanno I
    • Organizer
      Annual Meeting of the Japanese Society for Molecular Imaging
    • Place of Presentation
      Tokyo
    • Related Report
      2011 Final Research Report
  • [Presentation] -Real-time MRI of blood-brain barrier permeability of conventional therapeutics using nitroxides as spin-labels2009

    • Author(s)
      Zhelev Z., Bakalova R., Matsumoto K., Aoki I., Gadjeva V., Zheleva A., Anzai K., Kanno I.
    • Organizer
      4th European Molecular Imaging Meeting
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2011 Final Research Report
  • [Presentation] -Diagnostic Potential of Nitroxide Radicals in Cancer Using Magnetic Resonance Imaging Tomography2009

    • Author(s)
      Zhelev Z., Bakalova R., Saito S., Aoki I., Gadjeva V., Kanno I.
    • Organizer
      First International Workshop Antioxidants and Health Protection
    • Place of Presentation
      Stara Zagora, Bulgaria
    • Related Report
      2011 Final Research Report
  • [Presentation] Nitroxide radicals in brain imaging using T_1 weighted MRI2009

    • Author(s)
      Zhelev Z., Bakalova R., Matsumoto K., Aoki I., et al.
    • Organizer
      JSMI
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2009 Annual Research Report
  • [Presentation] Diagnostic potential of nitroxide radicals in cancer using MRI2009

    • Author(s)
      Bakalova R., Zhelev Z., Gadjeva V., Aoki I.
    • Organizer
      First International Workshop "Antioxidants and Health Protection"
    • Place of Presentation
      Stara Zagora, Bulgaria
    • Related Report
      2009 Annual Research Report
  • [Presentation] -EPR signal dynamic of several nitroxyl-labeled anticancer drugs in blood in vitro and in vivo2008

    • Author(s)
      Zhelev Z., K. Matsumoto, V. Gadjeva, A. Zheleva, R. Bakalova, I. Aoki, and K. Anzai
    • Organizer
      5th International Conference on Nitroxide Radicals SPIN' 2008
    • Place of Presentation
      Ancona, Italy
    • Related Report
      2011 Final Research Report
  • [Presentation] -Nitroxyl labels in brain imaging using T1-weighted MRI2008

    • Author(s)
      Zhelev Z., R. Bakalova, K. Matsumoto, I. Aoki, V. Gadjeva, K. Anzai, and I. Kanno
    • Organizer
      5th International Conference on Nitroxide Radicals SPIN' 2008
    • Place of Presentation
      Ancona, Italy
    • Related Report
      2011 Final Research Report
  • [Remarks] メディアによるアウトリーチ活動: NHK国際放送「効き目が見える抗がん剤」ラジオジャパン・フォーカス, 2009年5月18日(月)放送

    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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