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Cytotoxicity of Iodinated and Gadolinium-based Contrast Agents in Renal Tubular Cells at Angiographic Concentrations: In Vitro Study¹

¹ From the Institute of Diagnostic Radiology, University Hospital of Erlangen, Maximiliansplatz 1, 91054 Erlangen, Germany (M.C.H., S.K., M.S., M.B.H., M.U.); and Department of Medicine, Division of Nephrology and Hypertension (M.K.K.), and Department of Radiology (A.G.), Uni-versity Hospital of Saarland, Homburg/Saar, Germany. Received February 8, 2006; revision requested April 7; revision received April 28; final version accepted June 2. Address correspondence to M.C.H. (e-mail: Dr.MarcHeinrich{at}gmx.de).

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°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.

© RSNA, 2006