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Optimization of Perfluorochemical Levels with Radiation Therapy in Mice¹

Dana-Farber Cancer Institute [B. A. T., T. S. H., S. M. J.], and Joint Center for Radiation Therapy [T. S. H.], Boston, Massachusetts 02115

We have examined the effects of a wide range of levels of Therox, a perfluorochemical emulsion containing bis-perfluorobutyl ethylene (F44E) with carbogen breathing on the tumor growth delay of the Lewis lung carcinoma produced by single dose radiation and fractionated radiation. The enhancement in tumor growth delay with single dose radiation therapy increased as the dose of F44E was increased from 1.2 g/kg (0.03 ml) to 4 g/kg (0.1 ml). As the dose was increased further from 6 g/kg (0.15 ml) to 8 g/kg (0.2 ml) and then to 12 g/kg (0.3 ml), there was a progressive decrease in the tumor growth delay observed. The dose of 4 g/kg was the optimal F44E level with single dose radiation therapy, giving a dose modifying factor of 2.4 ± 0.2. This was true whether administered as a 48% (v/v) emulsion in 0.1 ml or as a 16% (v/v) emulsion in 0.3 ml. When the injection volume was varied from 0.1 ml to 0.4 ml at the 4 g/kg or 6 g/kg dose, thereby varying the emulsion concentration from 48% (v/v) to 12% (v/v) or 18% (v/v), the results tended to indicate that the volume of injection may be more important than the emulsion concentration, i.e., an injection volume of 0.2 ml produced the greatest tumor growth delay for both doses, and the emulsion concentration of 0.2 ml and 4 g/kg of F44E is 24% (v/v) whereas the emulsion concentration of 0.2 ml and 6 g/kg of F44E is 36% (v/v). Administering any dose of the emulsion with carbogen for 1 h prior to and during the radiation fraction on Day 1 only of a daily fractionated radiation protocol (3 Gy/fraction x 5 days) had very little effect on tumor growth delay compared to radiation and daily carbogen breathing. When F44E was administered on treatment Days 1, 3, and 5 with carbogen breathing, there was an increased effect on tumor growth delay which reached a maximum at 4 g/kg (0.1 ml) of 10.0 ± 1.2 days compared with 6.7 ± 1.0 days for radiation with daily carbogen breathing. However, when the F44E emulsion was administered every day with fractionated radiation and carbogen breathing, there was a marked enhancement in tumor growth delay observed across the entire dosage range, from 1.2 g/kg to 12 g/kg. The F44E dose response curve was very broad so that there was no significant difference in tumor growth delay observed (12.6 ± 1.5 days maximum) from a dose of 2 g/kg (0.05 ml) to a dose of 8 g/kg (0.2 ml). When F44E in the dosage range from 2 g/kg to 8 g/kg in a constant volume of 0.2 ml was administered in various schedules with daily fractionated radiation with carbogen breathing for 1 h prior to and during each fraction, the dose of 4 g/kg administered daily, again, produced the largest enhancement in tumor growth delay, 15.2 ± 1.4 days. Dose and injection volume appear to be the most important variables in achieving optimal tumor response with PFC emulsions.

¹ This work was supported by a grant from the E. I. Du Pont de Nemours & Co., Chemicals and Pigments Department, Deepwater, NJ.

² To whom requests for reprints should be addressed, at Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 9/28/88. Accepted 2/17/89.