Glucocorticoids modulate tumor radiation response through a decrease in tumor oxygen consumption

Purpose: We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO(2)) through inhibition of mitochondrial respiration. Experimental Design: The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO(2) was studied in murine TLT liver tumors and FSall fibrosarcomas. At the time of maximum pO(2) (t(max), 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO(2) measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging. Results: All glucocorticoids tested caused a rapid increase in pO(2). At t(max), tumor perfusion decreased, indicating that the increase in pO(2) was not caused by an increase in oxygen supply. Also at t(max), global oxygen consumption decreased. When irradiation (25 Gy) was applied at t(max), the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7). Conclusion: These results show the potential usefulness of the administration of glucocorticoids before irradiation.