Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by ¹⁹F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm³) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO₂) than their smaller counterparts (<1.5 cm³). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO₂, and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO₂ > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy.