Gadolinium Deposition Safety: Seeking the Patient’s Perspective

Abstract

G adolinium is a rare-earth metal of the lanthanide series; it is represented by the symbol Gd, and its atomic number is 64. 1,2 At room temperature, Gd is paramagnetic, meaning that it enhances nuclear relaxation rates, making it useful as a contrast agent for MR imaging. In clinical practice, Gd ions are administered to patients in the chelated form as gadolinium-based contrast agents (GBCA). 1,2 GBCA were first introduced in the late 1980s. Because of the intrinsic toxicity of Gd salts, initial clinical trials focused on the stability of the complex between the Gd ion and the chelating agent. Early studies pointed out that the stability constant was much higher for macrocyclic (or cryptelates, as they were initially called) than for linear agents. 1,3 These concerns never received much attention because all linear and macrocyclic agents appeared to be safe and well-tolerated. Moreover, because macrocyclic GBCA were only available in Europe and not in North America, there appeared to be little scientific incentive to study these concerns further. In fact, GBCA were considered so safe that they were used in large volumes as intra-arterial contrast agents for conventional angiography in patients with iodine allergy. 4 Indeed, double-dose GBCA were also commonly applied for gadolinium-enhanced MR angiography studies. These practices all changed in 2006, when a possible causation was identified between GBCA and nephrogenic systemic fibrosis (NSF). 5 NSF is characterized by fibrosis of the skin and internal organs, and the symptoms are somewhat reminiscent of scleroderma or scleromyxedema, though the underlying pathology is different. In this respect, credit should be given to Cowper et al 6 for a very early and brilliant description of NSF. The first cases of NSF had already been described earlier, but the possible causation between NSF and GBCA in patients with renal insufficiency was first reported in 2006. 5 Next, in 2006, the FDA restricted the use of GBCA in patients with a glomerular filtration rate of ,60 mL and ,15 mL/ min/1.73 m 2 ; 7 the cutoff then proposed in 2007 was ,30 mL/ min/1.72 m 2. Due to these measures, NSF has become very rare, and GBCA were, once again, considered very safe agents in patients with normal renal function.

Dentate-nucleus gadolinium deposition on magnetic resonance imaging: ultrasonographic and clinical correlates in multiple sclerosis patients

“…To date, no clear cause-effect relationship has been demonstrated in patients between brain gadolinium exposure and clinical consequences specific to neurological toxicity [ 36 ]. Especially, DN T1-hyperintensity was unrelated to the change of disease severity assessed on the EDSS [ 37 ].…”

Nanotechnology-Inspired Extracellular Vesicles Theranostics for Diagnosis and Therapy of Central Nervous System Diseases

“…The so-called Gd-infused hybrid EVs prolonged the retention of contrast and showed enhanced imaging and tumor specificity. This strategy could increase the safety of Gd applications, especially for brain imaging, given the concern of Gd unexpected CNS deposition . In addition, SPIONs are promising MRI contrast agents, exhibiting excellent biocompatibility, effectiveness, and degradability .…”

Current Perspectives on Clinical Use of Exosomes as a Personalized Contrast Media and Theranostics

“…Reduced Gd dosage, prolonged observation in the vasculature, no extravasation into surrounding tissue during dynamic imaging may increase the safety of gadolinium application, especially in the evidence of body and brain (mainly dentate nucleus and globus pallidus) gadolinium deposition after serial injection of nowadays commercially available gadolinium-based contrast agents [ 78 ].…”