Impact of gadolinium-based contrast agents on the growth of fish cells lines

Abstract

The present study was the first approach conducted under environmental concentrations of Gd-DOTA and Gd-DTPA-BMA to assess cellular impacts of these compounds. Gd-DOTA (Gadoteric acid) is one of the most stable contrast agent, currently used as Dotarem^® formulation during Magnetic Resonance Imaging exams. The study was mainly performed on a Zebra Fish cell line (ZF4; ATCC CRL-2050). At the concentrations of 0.127 nM and 63.59 nM (respectively 20 ng and 10 μg of Gd/L), we did not observed any toxicity of Dotarem^® but a slowdown of the cell growth was clearly measured. The effect is independent of medium renewing during 6 days of cell culturing. The same effect was observed i-with Gd-DOTA on another fish cell line (RT W1 gills; ATCC CRL-2523) and ii-with another contrast agent (Gd-DTPA-BMA - Omniscan^®) on ZF4 cells. On the ZF4 cell line, the diminution of the cell growth was of the same order during 20 days of exposure to a culture medium spiked with 63.59 nM of Dotarem^® and was reversible within the following 8 days when Dotarem^® was removed from the medium. As shown by using modified DOTA structure (Zn-DOTA), the effect may be due to the chelating structure of the contrast agent rather than to the Gd ion. Until now, the main attention concerning the impact of Gd-CA on living cells concerned the hazard due to Gd release. According to our results, quantifying the presence of Gd-CA chelating structures in aquatic environments must be also monitored.

Keywords: Cell growth; Contrast agent; Doratem(®); Gadolinium; Gadoteric acid; ZF4 cell line.