EPR Oxygen Images Predict Tumor Control by a 50% Tumor Control Radiation Dose

Abstract

Clinical trials to ameliorate hypoxia as a strategy to relieve the radiation resistance it causes have prompted a need to assay the precise extent and location of hypoxia in tumors. Electron paramagnetic resonance oxygen imaging (EPR O₂ imaging) provides a noninvasive means to address this need. To obtain a preclinical proof-of-principle that EPR O₂ images could predict radiation control, we treated mouse tumors at or near doses required to achieve 50% control (TCD₅₀). Mice with FSa fibrosarcoma or MCa4 carcinoma were subjected to EPR O₂ imaging and immediately radiated to a TCD₅₀ or TCD₅₀ ± 10 Gy. Statistical analysis was permitted by collection of approximately 1,300 tumor pO₂ image voxels, including the fraction of tumor voxels with pO₂ less than 10 mm Hg (HF10). Tumors were followed for 90 days (FSa) or 120 days (MCa4) to determine local control or failure. HF10 obtained from EPR images showed statistically significant differences between tumors that were controlled by the TCD₅₀ and those that were not controlled for both FSa and MCa4. Kaplan–Meier analysis of both types of tumors showed that approximately 90% of mildly hypoxic tumors were controlled (HF10%< 10%), and only 37% (FSA) and 23% (MCa4) tumors controlled if hypoxic. EPR pO₂ image voxel distributions in these approximately 0.5 mL tumors provide a prediction of radiation curability independent of radiation dose. These data confirm the significance of EPR pO₂ hypoxic fractions. The 90% control of low HF10 tumors argue that 0.5 mL subvolumes of tumors may be more sensitive to radiation and may need less radiation for high tumor control rates. Cancer Res; 73(17); 1–8. ©2013 AACR.