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

Abstract

Background

Earlier in vitro 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.

Methods

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.

Results

Ultra-low dose-rate irradiation decreased clonogenicity in hypoxic colorectal cancer cells. In vivo, 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.

Conclusion

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 in vivo.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by EU grant No. 222741 (METOXIA); Norges Forskningsråd (the Research Council of Norway); Kreftforeningen (the Norwegian Cancer Society) and Eckbos Legater.