Tissue pO₂ of Orthotopic 9L and C6 Gliomas and Tumor-Specific Response to Radiotherapy and Hyperoxygenation

Purpose

Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO₂) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO₂ in rats using a new and potentially widely useful method, multisite in vivo electron paramagnetic resonance oximetry.

Methods and Materials

Intracerebral 9L and C6 tumors were established in the left hemisphere of syngeneic rats, and electron paramagnetic resonance oximetry was successfully used for repeated tissue pO₂ measurements after 9.3 Gy of radiation and during carbogen breathing for 5 consecutive days.

Results

Intracerebral 9L gliomas had a pO₂ of 30–32 mm Hg and C6 gliomas were relatively hypoxic, with a pO₂ of 12–14 mm Hg (p < 0.05). The tissue pO₂ of the contralateral brain was 40–45 mm Hg in rats with either 9L or C6 gliomas. Irradiation resulted in a significant increase in pO₂ of the 9L gliomas only. A significant increase in the pO₂ of the 9L and C6 gliomas was observed in rats breathing carbogen, but this effect decreased during 5 days of repeated experiments in the 9L gliomas.

Conclusion

These results highlight the tumor-specific effect of radiation (9.3.Gy) on tissue pO₂ and the different responses to carbogen inhalation. The ability of electron paramagnetic resonance oximetry to provide direct repeated measurements of tissue pO₂ could have a vital role in understanding the dynamics of hypoxia during therapy that could then be optimized by scheduling doses at times of improved tumor oxygenation.

Glioma, Electron paramagnetic resonance oximetry, EPR oximetry, partial pressure of oxygen, pO₂, Radiotherapy, Carbogen