Influence of the 100% w/v perfluorooctyl bromide (PFOB) emulsion dose on tumour radiosensitivity

The radiosensitizing effect of a 100% w/v emulsion of a fluorocarbon, PFOB, which carries 4 times more oxygen than does Fluosol-DA 20% emulsion, was studied on two human tumour xenografts (HRT18 and HT29) and the murine tumour EMT6. This effect was compared with that obtained with carbogen alone. The fluorocrit (amount of fluorocarbon in the blood) and haematocrit remained unchanged from 7 to 65 min post-injection of the emulsion (8 ml/kg). Tumour-bearing mice were pretreated with 100% w/v PFOB emulsion doses ranging from 2 to 15 ml/kg in the presence of carbogen for 30 min prior to and during irradiation. The fluorocrit increased from 1.5% to 9.5% as the dose of 100% w/v PFOB emulsion increased from 2 to 15 ml/kg. The haematocrit remained the same for all the fluorocarbon emulsion doses used. Tumour radiosensitization varied with the fluorocarbon emulsion dose. Clinically relevant doses (2-4 ml/kg) of the 100% w/v PFOB emulsion plus carbogen produced significantly more radiosensitization than carbogen alone, with sensitizing enhancement ratios of 1.4 for EMT6 and 1.7 for HRT18. The radiosensitivity of HRT18 cells was thus very close to that obtained with normally oxygenated cells. For higher doses (8-15 ml/kg) the radiosensitizing effect of 100% w/v PFOB emulsion plus carbogen becomes comparable to that of carbogen alone. These experiments show that clinically useful doses of 100% w/v PFOB plus carbogen produced tumour radiosensitization only at relatively low fluorocrits. Thus the fluorocrit, and hence the fluorocarbon's oxygen-carrying capacity, is not the only factor involved in radiosensitizing tumour cells by oxygen-carrying fluorocarbon emulsions.