Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation

Numerous studies have demonstrated improvements in the oxygenation of tumor cells following both irradiation and carbogen breathing. The current studies were initiated to measure the combined effects of carbogen inhalation plus single and multi-dose irradiation on tumor oxygen availability, to better define the underlying physiological relationships.

Using KHT murine sarcomas, radiation was delivered to the tumor-bearing legs of non-anesthetized mice. Tumors were quick-frozen prior to or following single or multifraction irradiation and carbogen breathing, and intravascular HbO2 saturation profiles were determined cryospectrophotometrically.

HbO2 levels for blood vessels located near the tumor surface initially decreased following 10 Gy irradiation, then increased and remained elevated. Interior HbO2 levels remained unchanged. Following 2.5 Gy, HbO2 changes were minimal. At 24 h following 10 Gy, HbO2 levels were significantly increased compared to non-irradiated controls, and carbogen breathing produced no additional benefit. At 24 h following five fractions of 2 Gy, HbO2 levels throughout the tumor volume were significantly higher in carbogen breathing animals than in air breathing controls.

Although peripheral blood vessels demonstrated substantial improvements in oxygenation following irradiation, oxygen availability nearer the tumor center remained at very low levels. The utility of carbogen in enhancing tumor oxygen availability was maintained following five clinically relevant fractions. At higher doses, radiation-induced enhancements in HbO2 levels overshadowed the carbogen effect. For either air or carbogen breathing, a decrease in the percentage of vessels with very low oxygen content did not appear to be a major factor in the reoxygenation of the KHT tumor.