Perfluorochemicals and hyperbaric oxygen in radiation therapy.

It has been postulated that tumors contain hypoxic cells of decreased radiation sensitivity, which limit curability with radiation therapy. Hyperbaric oxygen has been used in an attempt to improve tumor oxygenation. The nature of the oxygen concentration-radiation sensitivity relationship (oxygen increases the slope of the radiation cell survival curve) suggests that a small number of hypoxic cells, as few as one in one million, would limit tumor curability. Oxygen moves by diffusion from the capillary into the tumor. An increase in partial pressure in the capillary will increase the effective diffusion distance. To improve tissue oxygenation effectively the partial pressure of oxygen in blood must be significantly increased throughout the length of the capillary, in particular at the venous end. Theoretical considerations indicate that hyperbaric oxygen as presently used in radiation therapy, 3 ATA, would lead to only marginal improvement. PartO2 may be as much as 0.8 atm below that of the inspired gas; this plus the consumption of oxygen along the length of the capillary lead to predictions of values for PEnd CapO2 of less than twice normal. Such considerations explain the rather limited success of hyperbaric oxygen with radiation therapy. Thus it is unnecessary to postulate an absence of hypoxic cells to explain this clinical observation. In the presence of perfluorocarbon micelles the non-hemoglobin-bound oxygen carrying capacity of blood is significantly increased. Theoretical considerations predict that the difference between PartO2 and PO2 of the inspired gas should be decreased. Furthermore, the nonhemoglobin-bound oxygen carrying capacity should be adequate to satisfy tissue consumption requirements without unloading hemoglobin, thereby avoiding the "PO2 buffering effect of hemoglobin" and permitting a significant increase in PO2 throughout the capillary length. This effect has been demonstrated using a rodent tumor model.