Synergistic combination of hyperoxygenation and radiotherapy by repeated assessments of tumor pO 2 with EPR oximetry

The effect of hyperoxygenation with carbogen (95% o 2 + 5% co 2) inhalation on rif-1 tumor po 2 and its consequence on growth inhibition with fractionated radiotherapy is reported. the temporal changes in the tumor po 2 were assessed by in vivo electron paramagnetic resonance (epr) oximetry in mice breathing 30% o 2 or carbogen and the tumors were irradiated with 4 gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. the rif-1 tumors were hypoxic with a tissue po 2of 5-9 mmhg. carbogen (cb) breathing significantly increased tumor po 2,with a maximum increase at 22.9-31.2 min on days 1-5,however,the magnitude of increase in po 2 declined on day 5. radiotherapy during carbogen inhalation (cb/rt) resulted in a significant tumor growth inhibition from day 3 to day 6 as compared to 30%o 2/rt and carbogen (cb/sham rt) groups. the results provide unambiguous quantitative information on the effect of carbogen inhalation on tumor po 2 over the course of 5 days. tumor growth inhibition in the cb/rt group confirms that the tumor oxygenation with carbogen was radiobiologically significant. repeated tumor po 2 measurements by epr oximetry can provide temporal information that could be used to improve therapeutic outcomes by scheduling doses at times of improved tumor oxygenation.