Correlation between Radiosensitivity, Percentage Hypoxic Cells and pO₂ Measurements in One Rodent and Two Human Tumor Xenografts

Computerized <tex-math>$p{\rm O}_{2}$</tex-math> histography has been used to measure the intratumor <tex-math>$p{\rm O}_{2}$</tex-math> in patients for the past few years, and there is now evidence that these tumors contain hypoxic cells. One of the major questions that remains to be answered is the relevance of such data to radiosensitivity. The present study looks for a correlation between intratumor <tex-math>$p{\rm O}_{2}$</tex-math>, the percentage of hypoxic cells in the tumor and the radiosensitization induced by carbogen and/or the oxygen carrier, perflubron emulsion. Two human tumor xenografts (HRT18, Na11+) and one rodent tumor (EMT6) were used. The radiosensitivity (clonogenic assay) and the oxygen tension (computerized <tex-math>$p{\rm O}_{2}$</tex-math> histography) were measured. All experiments were performed under similar conditions. Carbogen increased tumor radiosensitivity; sensitization was greatest when 4 ml/kg perflubron emulsion was used in conjunction with carbogen. The <tex-math>$p{\rm O}_{2}$</tex-math> distribution was shifted to higher <tex-math>$p{\rm O}_{2}$</tex-math> values in the tumors whatever the treatment; the shift was greater for perflubron emulsion plus carbogen. The low <tex-math>$p{\rm O}_{2}$</tex-math> values (<0.4 kPa) were lost for the HRT18 cells. A correlation (EMT6, HRT18) or a link (Na11+) between the radiosensitization and the oxygen tension measurements was found for values below 1.07 or 1.33 kPa. A trend between the percentage of hypoxic cells and <tex-math>$p{\rm O}_{2}$</tex-math> measurements was found taking into account <tex-math>$p{\rm O}_{2}$</tex-math> measurements comprised between 0.27 and 0.67 kPa.