Spatiotemporal measurement of tumor oxygenation reveals repeat hypoxic phenomenon in mice

Tumor hypoxia is considered a potential therapeutic problem because it reduces the effects of radiation therapy. Clinical experience has shown that long-term tumor oxygenation cannot be achieved with oxygen inhalation, but the mechanisms behind this phenomenon remain unknown. In this study, we designed an optical system for evaluating spatiotemporal changes in tissue oxygen tension (pO(2)) by phosphorescence quenching. The system can measure continuous changes in pO(2) at a fixed point and can also perform two-dimensional mapping of pO(2) in any part of the tumor tissue. We implanted tumor tissue in a dorsal skinfold chamber of C57BL/6 mice and observed tumor growth. After the tumor attained a diameter of 2 mm, the mice received oxygen inhalation and pO(2) was measured. Tumor pO(2) increased after inhalation but the oxygen level was not maintained despite continuous inhalation of pure oxygen; the tumor returned to a hypoxic state. These results mimic the clinical experience of oxygen inhalation treatment in radiation therapy. Our system reproduces the repeat hypoxic phenomenon in a murine tumor model and can be used to determine the mechanisms of oxygen metabolism in tumors.