Low dose-rate irradiation with [³H]-labelled valine to selectively target hypoxic cells in a human colorectal cancer xenograft model

<p><b>Background:</b> Earlier <i>in vitro</i> studies show that irradiation with an ultra-low dose-rate of 15 mGy/h delivered with [³H]-valine leads to loss of clonogenicity in hypoxic T-47D cells. Here, the aim was to determine if [³H]-valine could be used to deliver low dose-rate irradiation in a colorectal cancer model.</p> <p><b>Methods:</b> Clonogenicity was measured in cultured cancer cell line HT29 irradiated with 15 mGy/h combined with intermittent hypoxia. Mice with HT29 xenografts were irradiated by repeated injections of [³H]-valine intravenously. The activity in the tumor tissue was measured by scintillation counting and tumor growth, hypoxic fraction and tritium distribution within tumors were assessed by pimonidazole staining and autoradiography.</p> <p><b>Results:</b> Ultra-low dose-rate irradiation decreased clonogenicity in hypoxic colorectal cancer cells. <i>In vivo</i>, the tumor growth, hypoxic fraction and weight of the mice were similar between the treated and untreated group. Autoradiography showed no [³H]-valine uptake in hypoxic tumor regions in contrast to aerobic tissue.</p> <p><b>Conclusion:</b> Continuous low-dose-rate irradiation was well tolerated by aerobic tissue. This indicates a potential use of low dose-rate irradiation to target hypoxic tumor cells in combination with high dose-rate irradiation to eradicate the well oxygenated tumor regions. However, [³H]-valine is not the appropriate method to deliver ultra-low dose-rate irradiation <i>in vivo</i>.</p