Gadolinium retention in brain tissue linked to linear contrast agents

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The specific class of gadolinium-based contrast agents (GBCAs) used in prior contrast-enhanced MRI is a determining factor in whether patients exhibit heightened signal intensity on unenhanced T1-weighted MR images, according to study results published online April 6 in the journal Radiology.

Several recent studies have been published implicating gadolinium deposits as the cause of increased signal intensities in the brains of patients who have previously undergone repeated MRI scans using GBCAs. These agents can be divided into two distinct classes—linear and macrocyclic—and preventing the gadolinium from dissociating while in the body is critical to patient safety, as the heavy metal is cytotoxic to humans. “One mechanism underlying the potential toxic effects of GBCAs is the release of [gadolinium] from the complex and its deposition in tissues,” wrote lead author Alexander Radbruch, MD, JD, of the University of Heidelberg Medical Center in Germany, and colleagues. “This potential release of [gadolinium] depends on the stability of the GBCA in a biologic environment, the physicochemical properties, and the chemical structure of the gadolinium complex.”

Radbruch and his team set out to discover what difference, if any, the respective and repeated use of a linear GBCA or macrocyclic GBCA in previous MRI scans has on observed increases in signal intensity on unenhanced contrast. To do so, the researchers performed a retrospective analysis of two groups of 50 patients who had undergone six consecutive MRI examinations using either the linear GBCA gadopentetate dimeglumine or the macrocyclic GBCA gadoterate meglumine exclusively. Differences in patients’ mean signal intensity ratios of the dentate nuclues to pons and globus pallidus to thalamus on unenhanced T1-weighted images from the last and first examinations were calculated and compared.

Their results showed that despite a greater cumulative GBCA dose in the macrocyclic group, only the group who exclusively received the linear GBCA showed heightened signal intensities. “Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images are related to the serial application of the linear [GBCA],” wrote Radbruch and colleagues. “No significant [signal intensity] increase could be demonstrated after serial applications of the macrocyclic GBCA.” The increased signal activity also grew with cumulative dose in patients receiving the linear GBCA, while no intensity increase was observed in the macrocyclic group regardless of cumulative dose.

The researchers noted that only two of the nine GBCAs currently approved for use were evaluated in the study, but they believe their results should be cause for concern regarding continued and future use of the linear GBCAs in question and should spur additional research into the comparative effects of all GBCAs. “Even though no clinical implications can be drawn from the reported hyperintensities in the [dentate nucleus] and [globus pallidus], the findings are worrisome and should be taken into account when deciding whether to use gadopentetate dimeglumine,” wrote Radbruch and colleagues. “Future studies should be conducted to investigate whether this difference holds true for all linear and macrocyclic GBCAs.”