Enhancement of IUdR Radiosensitization in Cancer Therapy by Low-Energy Transmission X Ray Irradiation

2021 
5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.
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