Our previous studies have shown that
oxygen inhalation significantly reduces tumor hypoxia in the moderately well-differentiated HI subline of the Dunning prostate R3327 rat
carcinoma. To test our hypothesis that modifying
hypoxia could improve the radiosensitivity of these
tumors, we performed experimental
radiotherapy to compare the
tumor response to ionizing radiation alone or in combination with
oxygen inhalation.
Tumor pO(2) measurements were performed on size-selected
tumors several hours before
radiotherapy using (19)F nuclear magnetic resonance echo planar imaging relaxometry (FREDOM) of the reporter molecule
hexafluorobenzene. In common with our previous findings, the larger
tumors (>3.5 cm(3)) exhibited greater
hypoxia than the smaller
tumors (<2 cm(3); P < 0.001), and
oxygen inhalation reduced the hypoxic fraction (<10 Torr): In the larger
tumors, hypoxic fraction dropped significantly from a mean baseline value of 80% to 17% (P < 0.001). The effect of
oxygen administered 30 min before and during irradiation on
tumor response to a single 30-Gy dose of photons was evaluated by growth delay. For the smaller
tumors, no difference in growth delay was found when treatment was given with or without
oxygen breathing. By contrast, breathing
oxygen before and during irradiation significantly enhanced the growth delay in the larger
tumors (additional 51 days). The differential behavior may be attributed to the low baseline hypoxic fraction (<10 Torr) in small
tumors (20%) as a target for
oxygen inhalation. There was a strong correlation between the estimated initial pO(2) value and the radiation-induced
tumor growth delay (R > 0.8). Our histological studies showed a good match between the perfused vessels marked by
Hoechst 33342 dye and the total vessels immunostained by anti-CD31 and indicated extensive perfusion in this
tumor line. In summary, the present results suggest that the ability to detect modulation of
tumor pO(2), in particular, the residual hypoxic fraction, with respect to an intervention, could have prognostic value for predicting the efficacy of
radiotherapy.