Rapid Detection of Gadolinium-Based Contrast Agents in Urine with a Chelated Europium Luminescent Probe

Abstract

Gadolinium-based contrast agents are widely used in magnetic resonance imaging procedures to enhance image contrast. Despite their ubiquitous use in clinical settings, gadolinium is not an innocuous element, as suggested by several disorders associated with its use. Therefore, novel analytical technologies capable of tracking contrast agent excretion through urine are necessary for optimizing patient safety after imaging procedures. Here, we describe an assay to detect and quantify contrast agents in urine based on the luminescence quenching of a metal chelate probe, Eu3+–3,4,3-LI­(1,2-HOPO), which only requires 10 min incubation before measurement. Gadolinium-based contrast agents prevent the formation of the Eu3+–3,4,3-LI­(1,2-HOPO) complex, subsequently decreasing the luminescence of the assay solution. Three commercial contrast agents, Magnevist, Multihance, and Omniscan, were used to demonstrate the analytical concept in synthetic human urine, and subsequent quantification of mouse urine samples. To the best of our knowledge, this is the first assay capable of detecting and quantifying gadolinium-based contrast agents in urine without sample preparation or digestion.

Characterizing the general chelating affinity of serum protein fetuin for lanthanides

“…The emission of certain f-block elments can be sensitized by proteins with tyrosine-based binding sites through energy transfer mechanism [11,20]. Hence, the metal sensitization properties of fetuin were explored for the [Fetuin(Ln)4] complexes formed with Sm 3+ , Eu 3+ , Tb 3+ , and Dy 3+ ions, which are known to emit strong luminescence in the visible through antenna sensitization [18,[21][22][23]. The excitation spectrum of fetuin (Figure S2) shows a band centered at λmax = 280 nm, consistent with other tryptophan-rich proteins [24]; thus the luminescence spectra for all complexes were recorded under excitation at 280 nm.…”

Delineating toxicity mechanisms associated with MRI contrast enhancement through a multidimensional toxicogenomic profiling of gadolinium

“…9,10 Consequently, the U.S. Food and Drug Administration has issued a warning regarding retention of gadolinium after administration of GBCA (particularly with linear chelators, as opposed to macrocyclic chelating structures), 11 and the European Medicines Agency has recommended the suspension of another widely-used linear contrast agent, Magnevist, which is the N-methylglucamine salt of the gadolinium complex of diethylenetriamine pentaacetic acid. 12 As a result of these health concerns, new work has focused on improving the detection of gadolinium and GBCAs, 13,14 as well as on developing decorporation protocols to enhance their in vivo excretion. 15 Limited research, however, has been performed to understand the molecular origins of gadolinium toxicity: some studies characterized the inhibition growth of model organisms (e.g.…”

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials

“…Although the chemical similarities between these elements made their initial isolation and characterization a significant challenge, they now have unique applications in industry and medicine. Several lanthanides have become critical materials for many clean and sustainable energy technologies that will drive the future of our societies and are used, for example, in the production of batteries, magnets, motors, and other electronic components (4); low-concentration mixtures of lanthanides are used in Chinese agriculture to increase body weight gain among livestock (5,6); lanthanum carbonate (sold under the commercial name of Fosrenol) is a noncalcium phosphate binder used to control hyperphosphataemia (7); and gadolinium is employed in diagnostic medicine, as an essential component of MRI contrast agents (8,9).…”