Perfluorochemical Emulsions as Adjuncts to Radiotherapy

Abstract

Oxygen is a potent radiosensitizer. As virtually complete radiosensitization is observed at O₂ levels similar to those in venous blood, most healthy normal tissues exhibit essentially complete aerobic radiosensitivity. In contrast, solid tumors contain avascular areas and blood vessels which are subject to transient and persistent interruptions in blood flow; as a result, tumors contain viable cells existing under acute and chronic hypoxia. These hypoxic cells are resistant to radiation and to many drugs used in cancer therapy, and can limit the curability of tumors by conventional therapeutic regimens. Many laboratory and clinical studies are examining ways to circumvent the problem of hypoxic cells in cancer therapy. Studies reviewed here examine the effects of infusion of a perfluorochemical emulsion (PFC-E) combined with administration of O₂ at ambient or hyperbaric pressures on the radiation responses of solid tumors and of normal tissues which limit the intensity of therapy. Appropriate regimens of treatment with a PFC-E and oxygen-enriched atmospheres increase the radiation response of tumors, without severe host toxicities or corresponding increases in radiation injury to normal tissues. These studies show that PFC-E's have significant potential as adjuncts to radiotherapy and provide a basis for the design and initiation of clinical trials.