Perfluorochemicals attracted widespread attention in 1966, when Clark and Gollan showed that mice could survive for prolonged periods when completely immersed in liquid perfluorochemicals equilibriated with 02 at atmospheric pressure. The exceptional 02-carrying capacity of perfluorochemicals has provided the basis for testing these compounds for the perfusion of organs to be transplanted and as 02-transport fluids for use after hemorrhage or during surgery when blood transfusions are impossible or refused. Recent studies have shown that treatment with perfluorochemical emulsions and 02 can reduce ischemic myocardial damage after coronary artery occlusion, can protect against acute focal cerebral ischemia after ligation of the crebral artery, and can minimize injury after spinal cord compression. This is thought to reflect improved 02 delivery into the ischemic tissues, resulting from the unusual 02-transport capacity of the perfluorocarbons, perfluorochemical-induced changes in blood viscosity, and the small size of the micelles, which can enter-regions inaccessible to red blood cells. Solid tumors possess abnormal and insufficient vasculatures and, as a result, contain areas which are hypoxic because of transient or chronic deficiencies in blood flow. Hypoxic cells are very resistant to the cytotoxic effects of ionizing radiation and may limit the efficacy of radiotherapy in curing tumors. If administration of perfluorochemical emulsions and 02 can improve oxygenation in the hypoxic areas of tumors, in a manner analogous to that observed in other ischemic tissues, these agents may increase the radiosensitivity of some hypoxic tumor cells and improve the results of radiotherapy. This project will examine this hypothesis. EMT6 and KHJJ mouse mammary tumors and BA1112 rat rhabdomyosarcomas will be used to test the effects of perfluorochemical emulsions and 02-breathing on tumor cell survival curves, hypoxic fractions, and tumor cure. The effect of treatment with perfluorochemical emulsions on the efficacy of fractionated radiotherapy and chronic low dose rate irradiation will also be examined. The effect of the agents on the radiation response of 3 normal tissues (skin, gut, and bone marrow) will also be studied. These data will be used to calculate therapeutic ratios and assess the clinical potential of perfluorochemical emulsions as adjuncts to radiotherapy.
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