Intracellular hypoxia of tumor tissue estimated by noninvasive EPR oximetry technique using paramagnetic probes

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  • Matsumoto Atsuko
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A. Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Japan
  • Matsumoto Ken-ichiro
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A. Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Japan
  • Matsumoto Shingo
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.
  • Hyodo Fuminori
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A. Innovation Center for Medical Redox Navigation, Kyushu University
  • Sowers Anastasia L.
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.
  • Koscielniak Janusz W.
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.
  • Devasahayam Nallathamby
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.
  • Subramanian Sankaran
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.
  • Mitchell James B.
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.
  • Krishna Murali C.
    Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, U.S.A.

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タイトル別名
  • Intracellular Hypoxia of Tumor Tissue Estimated by Noninvasive Electron Paramagnetic Resonance Oximetry Technique Using Paramagnetic Probes

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Electron paramagnetic resonance (EPR) oximetry at 700 MHz operating frequency employing a surface coil resonator is used to assess tissue partial pressure of oxygen (pO2) using paramagnetic media whose linewidth and decay constant are related to oxygen concentration. Differences in extracellular and intracellular pO2 in squamous cell carcinoma (SCC) tumor tissue were tested using several types of water-soluble paramagnetic media, which localize extracellularly or permeate through the cell membrane. The nitroxide carboxy-PROXYL (CxP) can only be distributed in blood plasma and extracellular fluids whereas the nitroxides carbamoyl-PROXYL (CmP) and TEMPOL (TPL) can permeate cell membranes and localize intracellularly. EPR signal decay constant and the linewidth of the intravenously administered nitroxides in SCC tumor tissues implanted in mouse thigh and the contralateral normal muscle of healthy mice breathing gases with different pO2 were compared. The pO2 in the blood can depend on the oxygen content in the breathing gas while tissue pO2 was not directly influenced by pO2 in the breathing gas. The decay constants of CmP and TPL in tumor tissue were significantly larger than in the normal muscles, and lower linewidths of CmP and TPL in tumor tissue was observed. The SCC tumor showed intracellular hypoxia even though the extracellular pO2 is similar to normal tissue in the peripheral region.

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