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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Joubert
Aurélie
A
Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France.
Biston
Marie-Claude
MC
Boudou
Caroline
C
Ravanat
Jean-Luc
JL
Brochard
Thierry
T
Charvet
Anne-Marie
AM
Estève
François
F
Balosso
Jacques
J
Foray
Nicolas
N
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000528:radiation effects*; D007479:Iopamidol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D017356:Synchrotrons
D003287:Contrast Media; D004268:DNA-Binding Proteins; C057937:iomeprol; D004247:DNA; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D007479:Iopamidol