Tumour Oxygenation, Radiosensitivity, and Necrosis before and/or after Nicotinamide, Carbogen and Perflubron Emulsion Administration

Abstract

Hypoxia is one of the factors involved in tumour resistance to radiotherapy. One way to improve tumour oxygenation is to use oxygen carriers such as perflubron emulsion plus carbogen or vasoactive drugs such as nicotinamide. The perflubron emulsion and carbogen act mainly on hypoxia caused by limited diffusion of oxygen; nicotinamide acts mainly on acute hypoxia. The aim was to correlate radiosensitivity and pO₂ measurements (computerized pO₂ histograph) after nicotinamide, perflubron emulsion and carbogen administration, and to determine the role of necrosis in this correlation. Two human tumour xenografts (HRT18, Na11 +) and one rodent tumour (EMT6) were used. Clonogenic assays and pO₂ measurements were performed under similar conditions. The radiosensitization and oxygenation levels increased with all treatments. The maximal effects were found with the combination of nicotinamide (1 g/kg), perflubron emulsion and carbogen. A correlation between the radiosensitization and the pO₂ measurements was found for the three cell lines with a cut-off point of 10 mmHg. The presence of necrosis could explain the low pO₂ (<2 mmHg) found even when complete radiosensitization was observed.