Gadolinium deposition and the potential for toxicological sequelae – A literature review of issues surrounding gadolinium‐based contrast agents

Abstract

Every year, approximately 30 million magnetic resonance imaging scans are enhanced with gadolinium-based contrast agents (GBCAs) worldwide. Although the development of nephrogenic systemic fibrosis in patients with renal impairment is well-documented, over recent years it has become apparent that exposure to GBCAs can potentially result in gadolinium deposition within human bone and brain tissue even in the presence of normal renal function. This review will address some of the controversies surrounding the safety of GBCA administration based on evidence from in vivo experiments, animal studies and clinical studies. We additionally evaluate the potential risk of toxicity from exposure to gadolinium in light of new guidance published by the US Food and Drug Administration and the European Medicines Agency, and discuss whether gadolinium deposition disease exists as a new diagnosis.

Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging

“…Currently, marketed clinical magnetic resonance contrast agents are Gd chelates. It has recently been observed in humans and preclinical models that low levels of Gd can be detected in tissue, particularly in the central nervous system following administration of multiple doses of gadoliniumbased contrast agents (GBCA) [2][3][4]. While adverse health outcomes have not been associated with this retention, the observation has revived interest in MRI active chelates of biotic metals; candidates include manganese [5,6] and iron [7][8][9][10].…”

Increased signal intensity in the unenhanced T1-weighted magnetic resonance in the brain after repeated administrations of a macrocyclic-ionic gadolinium-based contrast agent

“…More than 30 million examinations are performed with GBCAs and more than 300 million doses are used each year worldwide [12,13]. Until Marckmann et al [14] reported that some GBCAs could cause nephrogenic systemic fibrosis (NSF) in patients with renal failure in 2006, GBCAs have been extremely popular in that they were safe.…”

Utilization of volumetric magnetic resonance imaging for baseline and surveillance imaging in Neuro-oncology

“…There are several advantages of performing volumetric imaging at baseline. First, it may negate the need for an additional MRI study to obtain the volumetric sequences necessary for either surgical or radiotherapy planning thereby saving the patient from a repeated, unnecessary second dose of gadolinium contrast medium, 4 and by reducing duplicate imaging which would be a cost saving for the NHS. Second, the inclusion of volumetric sequences in surveillance imaging protocols would allow the application of co-registration techniques, which have been shown to increase sensitivity in identifying pathological changes.…”