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- Title
Low dose-rate irradiation with [³H]-labelled valine to selectively target hypoxic cells in a human colorectal cancer xenograft model.
- Authors
Mikalsen, Stine Gyland; Mikalsen, Lars Tore Gyland; Sandvik, Joe Alexander; Aarnes, Eva-Katrine; Fenne, Siri; Flatmark, Kjersti; Lyng, Heidi; Edin, Nina Frederike Jeppesen; Pettersen, Erik Olai
- Abstract
Background: Earlier in vitro studies show that irradiation with an ultra-low dose-rate of 15mGy/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 15mGy/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 doserate 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.
- Subjects
ANIMAL experimentation; HYPOXEMIA; CELL culture; CELL lines; COLON tumors; RADIATION doses; RECTUM tumors; STAINS &; staining (Microscopy); VALINE; XENOGRAFTS; IN vivo studies
- Publication
Acta Oncologica, 2018, Vol 57, Issue 9, p1216
- ISSN
0284-186X
- Publication type
Article
- DOI
10.1080/0284186X.2018.1457223