Use of a perfluorochemical emulsion to improve oxygenation in a solid tumor

The ability of the perfluorochemical emulsion, Fluosol-DA, to oxygenate the naturally-occurring hypoxic cells of solid tumors was examined. BALB/c mice bearing EMT6 mouse mammary tumors were given in a single i.v. injection of 0.015 ml/g of Fluosol, and were then treated with 95% O2/5% CO2 for 30 min before irradiation with graded doses of X rays. The pretreatment increased the cytotoxic effect of the radiation, as assayed by colony formation in vitro. The dose-response curve for the combination regimen was parallel to that for radiation alone, but was offset towards lower survivals. This change is consistent with the change which would be expected if the pretreatment decreased the proportion of hypoxic cells in the tumors. Studies with unoxygenated perfluorochemical emulsions in vivo and in vitro and studies with O2/CO2 alone in vivo suggested that the survival curve changes did not reflect either direct cytotoxic effects of the perfluorochemical emulsion or the O2/CO2-breathing, or radiosensitizing or physiologic effects of either agent alone. The data reported here suggest that oxygenated perfluorochemical emulsions may decrease the proportion of hypoxic cells in solid animal tumors and encourage further preclinical evaluation of these agents as potential adjuvants to radiotherapy.