Oxygen-Sensitive MRI: A Predictive Imaging Biomarker for Tumor Radiation Response?

PURPOSE To develop a non-invasive prognostic imaging biomarker related to hypoxia to predict stereotactic ablation radiation therapy (SAbR) tumor control. METHODS AND MATERIALS One hundred and forty-five subcutaneous syngeneic Dunning prostate R3327-AT1 rat tumors were focally irradiated once using CBCT guidance on a small animal irradiator at 225 kV. Various doses in the range 0-100 Gy were administered, while rats breathed air or oxygen and tumor control was assessed up to 200 days. Oxygen-sensitive MRI (T1-weighted, ΔR1, ΔR2*) was applied to 79 of these tumors at 4.7 T to assess response to an oxygen gas breathing challenge on the day before irradiation as a probe of tumor hypoxia. RESULTS Increasing radiation dose in the range 0-90 Gy enhanced tumor control of air-breathing rats with a TCD50 estimated at 59.6±1.5 Gy. Control was significantly improved at some doses when rats breathed oxygen during irradiation (e.g., 40 Gy, p 0.922 with O2-gas breathing challenge showed significantly better control at 40 Gy, when irradiated while breathing oxygen (75% vs. 0%, p 0.922 revealed different survival curves with TCD50=36.2±3.2 Gy for tumors responsive to oxygen gas breathing challenge, which was significantly less than 54.7±2.4 Gy for unresponsive tumors (p<0.005), irrespective of the gas inhaled during tumor irradiation. CONCLUSIONS Oxygen-sensitive MRI allowed stratification of tumors in terms of local control at 40 Gy, indicating a potential predictive imaging biomarker. Increasing dose to 50 Gy overcame radiation resistance attributable to hypoxia in 50% of tumors.