Evidence for macrophage involvement in the enhancement of tumor growth delay with X-ray/Fluosol-DAR/O2 combination therapy

The perfluorochemical emulsion, Fluosol-DAR, in combination with breathing a 95% oxygen atmosphere, has been shown to enhance the response of several solid tumors to radiation treatment. In this study, the number of macrophages present in two murine tumors was assessed in the absence of Fluosol-DA treatment and at various times post-Fluosol-DA treatment using a rosetting assay. The number of macrophages in the Lewis lung carcinoma and the FSaII fibrosarcoma, after an initial decrease, increased nearly 2-fold (at 14 days) after a single Fluosol-DA injection. Tumor response was assessed by tumor growth delay and excisional tumor cell survival assays in two tumor systems. Greater dose modifying effects were consistently observed when tumors remained in situ. Some animals were treated with carrageenan, a macrophage poison, prior to implantation of Lewis lung tumor. Animals treated with carrageenan, Fluosol-DA and carbogen prior to and during X-ray treatment exhibited a dose modifying factor (DMF) of 1.74 +/- 0.08. Animals treated similarly but without carrageenan pretreatment demonstrated a DMF of 2.61 +/- 0.22. Fluosol-DA administered 24 hours prior to carbogen breathing and X-rays resulted in a greater tumor growth delay than when the perflorochemical was injected immediately prior to radiation/carbogen treatment. The relatively nonimmunogenic FSaII tumor/C3H/Sed host system gave similar results but instead of dose modification, parallel displacements in the dose response curves were seen. Again, Fluosol-DA administrated 24 hours prior to radiation was more effective in sensitizing the tumor than immediate administration. These results suggest that Fluosol-DA in addition to functioning as an oxygen-carrier produces a nonspecific activation of the immune system.