Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: In vitro study

Purpose: To test in vitro whether gadolinium-based contrast agents induce fewer toxic effects on renal tubular cells than does an iodinated contrast medium at concentrations used for angiography. Materials and Methods: LLC-PK1 cells were incubated with iomeprol, gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, gadodiamide, and corresponding mannitol solutions for 24 hours at 37 degrees C in two experimental settings: measurements with equally attenuating solutions and measurements with equimolar solutions. Cytotoxicity was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, trypan blue testing, and an assay to detect apoptosis and necrosis. Data were analyzed with analyses of variance and post hoc tests. Results: Yielding the same x-ray attenuation, iomeprol-300 and iomeprol-150 at concentrations of 2.34-18.75 mg of iodine per milliliter induced significantly (P <.001) lower inhibition of MTT conversion (74%-102% of undamaged control cells) compared with 15.63-125.00 mmol/L concentrations of the gadolinium-based agents (mean percentages of undamaged control cells: 48%-80%, 50%-87%, 60%-95%, and 56%-92% with gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, and gadodiamide, respectively). At equimolar concentrations (62.5 mmol/L), iomeprol-190 induced a mean extent of inhibition of MTT conversion (69% of undamaged control cells) similar to that induced by gadoterate meglumine (71%) and gadodiamide (70%), whereas gadopentetate dimeglumine and gadobenate dimeglumine induced stronger effects (63% and 64%, respectively; P <.001). At trypan blue testing, there were more dead cells after incubation with 125 mmol/L gadopentetate dimeglumine than after incubation with iomeprol-190 (57% vs 19%, P <.001). The 125 mmol/L gadopentetate and gadobenate formulations induced more necrosis and apoptosis than did gadoterate meglumine, gadodiamide, and iomeprol ( mean percentage difference between treated and untreated control cells: for necrosis, +124%, +95%, +17%, -6%, and +3%, respectively; for apoptosis, +34%, +35%, +13%, +4%, and +5%, respectively; P <.001). Conclusion: At angiographic concentrations, gadolinium-based contrast agents do not induce fewer cytotoxic effects on cultured renal tubular cells than does iomeprol. (c) RSNA, 2006.