Brurberg, K. G., Thuen, M., Ruud, E. B. M. and Rofstad, E. K. Fluctuations in pO2 in Irradiated Human Melanoma Xenografts. Radiat. Res. 165, 16–25 (2006).
Several studies have demonstrated that untreated tumors may show significant fluctuations in tissue oxygen tension (pO2). Radiation treatment may induce changes in the tumor microenvironment that alter the pO2 fluctuation pattern. The purpose of the present study was to investigate whether pO2 fluctuations may also occur in irradiated tumors. A-07 human melanoma xenografts were irradiated with single doses of 0, 5 or 10 Gy. Fluctuations in pO2 were recorded with OxyLite probes prior to irradiation and 24 and 72 h after the radiation exposure. Radiation-induced changes in the tumor microenvironment (i.e. blood perfusion and extracellular volume fraction) were assessed by dynamic contrast-enhanced magnetic resonance imaging. Seventy-two hours after 10 Gy, tumor blood perfusion had decreased to ∼40% of that prior to irradiation, whereas the extracellular volume fraction had increased by ∼25%. Fluctuations in pO2 were seen in most tumors, irrespective of radiation dose and time after irradiation. The mean pO2, the number of fluctuations around the mean pO2, the number of fluctuations around threshold pO2 values of 1, 2, 3, 5, 7 and 10 mmHg, and the amplitude of the fluctuations were determined for each pO2 trace. No significant differences were detected between irradiated and unirradiated tumors. The results showed that pO2 fluctuations may occur in irradiated tumors and that the pO2 fluctuation pattern in A-07 tumors exposed to 5 or 10 Gy is similar to that in untreated tumors. Consequently, these doses did not induce changes in the tumor microenvironment that were sufficient to cause detectable alterations in the pO2 fluctuation pattern.