Molecular Imaging of the Tumor Microenvironment Reveals the Relationship between Tumor Oxygenation, Glucose Uptake, and Glycolysis in Pancreatic Ductal Adenocarcinoma

  • Kazutoshi Yamamoto
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Jeffrey R. Brender
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Tomohiro Seki
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Shun Kishimoto
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Nobu Oshima
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Rajani Choudhuri
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Stephen S. Adler
    2Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, NCI, Frederick, Maryland.
  • Elaine M. Jagoda
    3Molecular Imaging Program, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Keita Saito
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Nallathamby Devasahayam
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Peter L. Choyke
    3Molecular Imaging Program, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • James B. Mitchell
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Murali C. Krishna
    1Radiation Biology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.

抄録

<jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>Molecular imaging approaches for metabolic and physiologic imaging of tumors have become important for treatment planning and response monitoring. However, the relationship between the physiologic and metabolic aspects of tumors is not fully understood. Here, we developed new hyperpolarized MRI and electron paramagnetic resonance imaging procedures that allow more direct assessment of tumor glycolysis and oxygenation status quantitatively. We investigated the spatial relationship between hypoxia, glucose uptake, and glycolysis in three human pancreatic ductal adenocarcinoma tumor xenografts with differing physiologic and metabolic characteristics. At the bulk tumor level, there was a strong positive correlation between 18F-FDG-PET and lactate production, while pO2 was inversely related to lactate production and 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) uptake. However, metabolism was not uniform throughout the tumors, and the whole tumor results masked different localizations that became apparent while imaging. 18F-FDG uptake negatively correlated with pO2 in the center of the tumor and positively correlated with pO2 on the periphery. In contrast to pO2 and 18F-FDG uptake, lactate dehydrogenase activity was distributed relatively evenly throughout the tumor. The heterogeneity revealed by each measure suggests a multimodal molecular imaging approach can improve tumor characterization, potentially leading to better prognostics in cancer treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>Novel multimodal molecular imaging techniques reveal the potential of three interrelated imaging biomarkers to profile the tumor microenvironment and interrelationships of hypoxia, glucose uptake, and glycolysis.</jats:p> </jats:sec>

収録刊行物

  • Cancer Research

    Cancer Research 80 (11), 2087-2093, 2020-06-01

    American Association for Cancer Research (AACR)

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参考文献 (21)*注記

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