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.