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

Abstract

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.

• Authors: Marc C Heinrich, Martin K Kuhlmann, Sonja Kohlbacher, Mario Scheer, Aleksandar Grgic, Martina B Heckmann, Michael Uder
• Journal: Radiology (Radiology) Vol. 242 Issue 2 Pg. 425-34 (Feb 2007) ISSN: 0033-8419 [Print] United States
• PMID: 17179401 (Publication Type: Comparative Study, Journal Article)
• Copyright: (c) RSNA, 2007.

Chemical References

• Coloring Agents
• Contrast Media
• Organometallic Compounds
• Tetrazolium Salts
• Thiazoles
• gadobenic acid
• iomeprol
• Mannitol
• Meglumine
• gadodiamide
• Iodine
• Gadolinium
• thiazolyl blue
• Trypan Blue
• Iopamidol
• Gadolinium DTPA
• gadoterate meglumine

Topics

• Angiography
• Animals
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Coloring Agents
• Contrast Media (administration & dosage, toxicity)
• Gadolinium (administration & dosage, toxicity)
• Gadolinium DTPA (administration & dosage, toxicity)
• Iodine (administration & dosage, toxicity)
• Iopamidol (administration & dosage, analogs & derivatives, toxicity)
• Kidney Tubules, Proximal (cytology, drug effects)
• LLC-PK1 Cells
• Mannitol (toxicity)
• Meglumine (administration & dosage, analogs & derivatives, toxicity)
• Necrosis
• Organometallic Compounds (administration & dosage, toxicity)
• Swine
• Tetrazolium Salts
• Thiazoles
• Trypan Blue