Preclinical studies of a perfluorochemical emulsion as an adjunct to radiotherapy

Abstract

Tumor growth and tumor cell survival endpoints were used to examine the effects of a perfluorochemical emulsion, Fluosol-DA, 20%, and carbogen (95% O 2/5% CO 2) On EMT6 mouse mammary tumors in BALB/c mice. These studies defined the effects of the Fluosol dose on the hematocrit and fluorocrit of the mice and on the radiation response of the tumors. The effect of varying the duration of carbogen breathing before irradiation was examined; times of 5–60 min gave similar enhancements of tumor radiosensitivity. Potentiating effects were not observed when the tumors were irradiated 1–3 days after Fluosol injection, probably reflecting the observed clearance of the perfluorochemicals from the circulating blood. Fluosol injected 30 min-2 days before irradiation did not alter the radiation response of tumors in air-breathing or N 2-asphyxiated mice. Together, these studies provided additional support for the hypothesis that the potentiation of tumor radiation response observed after treatment with Fluosol plus carbogen results from changes in O 2 delivery to the hypoxic tumor cells by oxygenated perfluorochemical particles. This confirms the conclusion drawn on the basis of the observed changes in the tumor cell survival curve. Studies of tumor cell survival, tumor cell yield, tumor growth, and artificial lung metastasis formation revealed no effects of Fluosol treatment (without irradiation) on tumor progression or metastasis. Studies examining the effects of Fluosol plus carbogen on the growth of tumors irradiated with 5 Gy showed that the changes in tumor radiosensitivity observed using cell survival endpoints also occurred in tumors left in situ after irradiation with a radiation dose similar to those used in some clinical trials.