Incorporation of excess gadolinium into human bone from medical contrast agents

Magnetic Resonance Imaging

Jay

et al. 2016

103

a b s t r a c t a r t i c l e i n f oGadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known.

“…Gadolinium presence was originally observed in bone [5,6,30] and more recently in the brain [7][8][9][31][32][33][34][35][36][37][38][39] in patients with normal renal function.…”

Section: Gadolinium Storage Conditionmentioning

confidence: 97%

Gadolinium toxicity and treatment

Magnetic Resonance Imaging

Jay

et al. 2016

103

“…gadobutrol and gadoteridol) and linear chelators in patients with normal renal function [10]. Gadolinium retention in bone and skin had already been described by histology studies [11,12], and very recent data based on autopsy studies suggest that gadolinium can accumulate in other organs as well, such as the liver and kidney [13,14].…”

Section: Evidence For Gadolinium Retentionmentioning

confidence: 99%

Gadolinium retention after administration of contrast agents based on linear chelators and the recommendations of the European Medicines Agency

2017

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) earlier this year recommended to suspend some marketing authorisations for Gadolinium Containing Contrast Agents (GCCAs) based on linear chelators due to the potential risk of gadolinium retention in the human body. These recommendations have recently been re-evaluated by EMA's Committee for Medicinal Products for Human Use (CHMP), and confirmed the final opinion of the European Medicines Agency. This editorial provides an overview of the available GCCAs and summarises the recent evidence of gadolinium retention. Moreover, a critical appraisal of the strengths and limitations of the scientific evidence currently available on gadolinium retention is given. Key points • EMA recommended suspension of some EU marketing authorisations of four linear GCCAs. • Brain MRI findings indicating gadolinium retention have been confirmed by mass spectrometry.• Current scientific evidence for gadolinium retention has several methodological limitations.• No clear clinical evidence exists indicating that gadolinium retention causes neurotoxicity.• Long-term safety of GCCAs, however, remains unclear.

“…Even in patients with normal renal function, in vivo clinical exposure to gadolinium chelates results in gadolinium incorporation into body tissues such as bone matrix [54][55][56] or brain tissues. 26,27 As early as 1991, Rocklage et al 57 stated, "Minute amounts of chelated or unchelated metals are likely to remain in the body for an extended period and could possibly result in a toxic effect."…”

Section: Gadolinium Retention and Tissue Depositionmentioning

confidence: 99%

Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update

Semelka

American Journal of Neuroradiology

et al. 2015

373

244

SUMMARY:In current practice, gadolinium-based contrast agents have been considered safe when used at clinically recommended doses in patients without severe renal insufficiency. The causal relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with renal insufficiency resulted in new policies regarding the administration of these agents. After an effective screening of patients with renal disease by performing either unenhanced or reduced-dose-enhanced studies in these patients and by using the most stable contrast agents, nephrogenic systemic fibrosis has been largely eliminated since 2009. Evidence of in vivo gadolinium deposition in bone tissue in patients with normal renal function is well-established, but recent literature showing that gadolinium might also deposit in the brain in patients with intact blood-brain barriers caught many individuals in the imaging community by surprise. The purpose of this review was to summarize the literature on gadolinium-based contrast agents, tying together information on agent stability and animal and human studies, and to emphasize that low-stability agents are the ones most often associated with brain deposition.ABBREVIATIONS: DN ϭ dentate nuclei; GBCA ϭ gadolinium-based contrast agent; NSFϭ nephrogenic systemic fibrosis