Irradiation in presence of iodinated contrast agent results in radiosensitization of endothelial cells: consequences for computed tomography therapy.

Abstract

To date, iodinated contrast agents (ICA) are commonly used in medical imaging to improve tumor visualization by attenuating scanners X-rays. However, some adverse reactions to ICAs are still reported, and their molecular origin remains unclear. In 1983, it was proposed to visualize and treat ICA-loaded tumors by using scanners as therapy machines to enhance X-rays absorption at the iodine atoms. Theoretically, such physical conditions are optimized at 50 keV and can be easily obtained with synchrotrons. Here, we examined the molecular and cellular responses of mammalian endothelial cells to radiation in the presence of iomeprol, one of the most extensively used ICAs. Irradiation with X-rays at 50 keV in the presence of iomeprol produced a strong radiosensitization effect. The same conclusion was reached with a standard medical irradiator but to a lesser extent. While such treatment did not produce additional DNA double-strand breaks, we observed a dose-dependent production of iodides due to the iomeprol radiolysis that inhibit double-strand break repair rate by decreasing DNA-PK kinase activity. Our data suggest that the concomitant use of ICA and radiation may be toxic when radiation-produced iodide concentrations and double-strand break yields are sufficient. The potential toxicity of ICAs during X-rays for diagnosis and therapy is discussed.