Effect of Dose, Schedule, and Rate of Administration on Radiosensitization by a High‐Concentration Perflubron Emulsion/Carbogen

Perfluorochemical emulsions are highly biocompatible materials which carry and deliver oxygen when a high oxygen content atmosphere is breathed. The concentrated perflubron emulsion Oxygent™CA (Oxygent) used in the current study is a second generation perfluorocarbon emulsion which is much more stable and much more concentrated (90% w/v perflubron) than the earlier preparations. In combination with single dose radiation, a range of Oxygent doses corresponding to perfluorochemical levels from 4 to 12 g/kg led to dose modifying factors from 1.2 to 1.9, respectively. With daily fractionated radiation and daily Oxygent administration over the same dosage range, dose modifying factors from 1.4 to 2.1 were achieved. In general, administration of Oxygent prior to each radiation fraction produced the greatest enhancement in tumor response, although the highest dose of Oxygent administered (12 g/kg) on alternate days with daily carbogen breathing produced a comparable tumor growth delay to 4 g/kg of the perfluorochemical emulsion administered daily with carbogen breathing. Rapid administration of the emulsion was necessary to achieve maximal enhancement of tumor growth delay from this therapeutic adjuvant. These results indicate that dose, schedule of administration, and rate of infusion are important variables to consider in the design of clinical trials to maximize the therapeutic benefit achievable with perfluorochemical emulsions as adjuvants to radiation therapy. © 1993 Wiley‐Liss, Inc.