Tumor growth and
tumor cell survival endpoints were used to examine the effects of a perfluorochemical
emulsion,
Fluosol-DA, 20%, and
carbogen (95% O2/5% CO2) 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 N2-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 O2 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.