Effect of oxygen level on the enhancement of tumor response to radiation by perfluorochemical emulsions or a bovine hemoglobin preparation

Abstract

Attempts to correct tumor hypoxia with oxygen-carrying solutions have used high concentrations of inspired oxygen (FiO2 100% or 95%). In the clinic, however, obtaining such high levels of FiO2 using mask ventilation in older patients or in children may be difficult. Since lower levels of FiO2 had not been previously tested, we examined the antitumor efficacy of FiO2 levels of 65, 85, and 95% breathed for 1 hr prior to and during irradiation used with the concentrated perfluorochemical emulsion F44E, the less concentrated emulsion, Fluosol-DA, or a new preparation consisting of purified bovine hemoglobin solution, PBHS. When tested in mice bearing the Lewis lung carcinoma with 2, 3, or 4 Gy daily for 5 days, daily Fluosol-DA produced only a small increase in the slope of the tumor growth delay versus irradiation alone, when used with 85% FiO2 (dose modifying factor [DMF] 1.3), but produced a DMF of 2.1 with 95% FiO2. Various concentrations of F44E (2, 4, or 8 g PFC/kg) each required a 95% FiO2 for full effect but the 8 g/kg dose had a discernable effect with an FiO2 of 65% and 85% (DMF 1.25 and 1.30, respectively). For PBHS, in contrast, a DMF of 1.6 was observed at 20% FiO2, but surprisingly this increased further to 2.1 with 95% FiO2. Further investigations of PBHS with irradiation demonstrated that daily administration of PBHS (12 ml/kg) 1 hr before single Xray fractions of 5, 10, 15, or 20 Gy with 20% FiO2 resulted in a DMF of 1.6-1.7 in the FSaIIC fibrosarcoma compared with irradiation alone when ascertained by tumor cell excision assay. These results indicate that to achieve maximum antitumor benefit with these oxygen-carrying solutions with radiation therapy, care must be taken to insure that FiO2 levels near 100% are achieved.