Cellular toxicities of gadolinium-based contrast agents used in magnetic resonance imaging.

Contrast agents have been used in magnetic resonance imaging (MRI) as a radiological method. Gadolinium-based contrast agents (GBCAs), because of their paramagnetic characteristics, are the ones mostly used in MRI to increase signal intensity. However, the use of contrast media has raised concerns on cellular toxic risks of these agents. Studies showed the accumulation of gadolinium after injection to humans with or without renal impairment. Also, there are findings obtained under in vitro and/or in vivo conditions that revealed conflicting results for their cytotoxic and genotoxic effects. Some of them declared damage in cells and genetic material; some others did not. Abnormal cell growth and genetic aberration are critical because they may lead to carcinogenesis in somatic cells or may be transferred to the next generations through germ cells. Therefore, understanding the effect of GBCAs on cells is important for their safer usage in clinical administrations to generate high-quality contrast-enhanced magnetic resonance images. Because of all these reasons, cellular toxicities-mainly genotoxic and cytotoxic effects-of GBCAs were reviewed in this paper.

Genotoxic effects of gadobutrol and gadoversetamide active substances used in magnetic resonance imaging in human peripheral lymphocytes in vitro.

Gadobutrol and gadoversetamide are gadolinium-based contrast agents (GBCAs) widely used during magnetic resonance imaging examination. In this study, the genotoxicity of two GBCAs, gadobutrol and gadoversetamide, was investigated by using different endpoints: chromosome aberration (CAs), sister chromatid exchange (SCEs), and micronucleus (MNi). Human peripheral lymphocytes (PBLs) were treated with five concentrations (7 000, 14 000, 28 000, 56 000, and 112 000 µg/mL) of both agents. While a few concentrations of gadobutrol significantly increased abnormal cell frequency and CA/Cell, nearly all the concentrations of gadoversetamide significantly elevated the same aberrations. Similarly, the effect of gadoversetamide on the formation of SCEs was higher than those of gadobutrol. Only one concentration of gadoversetamide significantly increased MN% but no gadobutrol. The comet assay was applied for the only gadobutrol which induced a significant increase in tail intensity at the highest concentration only. On the other hand, significantly decreased mitotic index (MI) was observed following both substances, again gadoversetamide was slightly higher than those of the gadobutrol. The results revealed that both the contrast agents are likely to induce genotoxic risk in PBLs. However, different concentrations and treatment periods should be examined in vitro and specifically in vivo with different test systems for the safer usage of these contrast agents.