BACKGROUND: Gadolinium-based contrast agents (GBCAs) increase the sensitivity and clinical utility of magnetic resonance imaging (MRI) examinations and are used extensively worldwide. While concerns remain regarding the potential toxicity of retained gadolinium (Gd) based on "elevated" serum or urinary Gd concentrations, current Gd reference intervals were established in GBCA-naive patients with normal renal function. Therefore, the aim of this study was to determine the serum and urine Gd clearance in patients with normal renal function after being administered intravenous gadobutrol for a contrast-enhanced MRI examination. METHODS: Patients with normal renal function (estimated glomerular filtration rate ≥60 mL/min) with no prior GBCA exposure in the past 6 months were enrolled and had blood and urine collected before and ~1, 3, 7, 14, 28, 56, and 84 days after their gadobutrol-enhanced MRI examination to measure Gd at each time point. Serum and urine Gd were quantified using a clinically validated inductively coupled plasma mass spectrometry-based assay with a limit of quantitation of 0.1 ng/mL (μg/L). RESULTS: Thirty-one patients who underwent a gadobutrol-enhanced MRI were enrolled, and 24 completed all collection time points. The pharmacokinetic data suggested a multicompartment (5 phase) model of elimination where 95% of patient's serum Gd fell below the unexposed reference interval (<
0.5 ng/mL) at ~56 days and 95% of urine Gd would fall below the unexposed reference interval (<
0.8 μg/g creatinine) at ~132 days. Based on review of the electronic medical record, none of the patients self-reported any Gd-related toxicity. CONCLUSIONS: Current reference intervals for serum and urinary gadolinium clearance are not applicable for patients in the 5 months following intravenous gadobutrol exposure.