Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation

Abstract

Purpose : To determine whether electrode measurements of tumor oxygenation, made in a variety of murine tumor models, correlate with estimates of radiobiological hypoxia in the same tumor systems. Methods and Materials : The tumor models used were a C3H mammary carcinoma grown in the feet of CDF1 mice; the SCCVII, KHT and RIF-1 tumors grown in the feet or flanks of C3H/Km mice; and the CaNT and SaF tumors grown on the backs of CBA mice. All treatments were performed when tumors were about 200 mm 3 in size. Radiobiological hypoxic fractions were determined using either a paired survival curve assay, with survival measured 0–24 h after irradiation, or using a clamped tumor control assay, with percent local tumor control estimated 90 days after treatment. Measurements of tumor oxygen partial pressure (pO2) distributions were performed using Eppendorf oxygen electrodes. Results : The hypoxic fractions determined from the radiation response data were about 1% in RIF-1 and SCCVII, 12% in C3H and KHT, 28% in CaNT and up to 38% in SaF tumors. When this data was compared with the tumor oxygenation measurements it was found that as hypoxic fraction increased the mean, median, and the percentage of pO 2 values ≤ 5 mmHg showed a trend towards poorer oxygenation status. However, none of these pO 2 changes were significantly correlated with hypoxia. Moreover, the pO 2 values ≤ 2.5 mmHg indicated an improvement in oxygen status with increasing hypoxic fraction. Conclusion : Electrode measurements of tumor oxygenation alone may, therefore, not be a good indicator of tumor hypoxia across different tumor cell lines.