Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution

Abstract

Gadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.

Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals following contrast agent administration

“…Although gadolinium can be retained in the kidneys after GBCA administration, there is a concern that reduced clearance of GBCAs by the kidneys due to renal dysfunction, could result in increased residence time of GBCAs in the body and subsequent higher retention of gadolinium. Proximal tubular vacuolation has been demonstrated in animals treated with GBCAs (Elmståhl et al 2007 ; McDonald et al 2017b ; Do et al 2020 ). This vacuolation phenomenon presents as lipid rich vacuoles with electron dense structures, with gadolinium deposits lining the lipid deposits in the renal proximal tubule (Do et al 2020 ).…”

Gadobutrol-induced acute respiratory distress syndrome rescued by intravenous immunoglobulin and extracorporeal membrane oxygenation

“…In addition to traditional treatment of allergy, IVIG is also effective for treating life-threatening non-IgEmediated allergy. In previous studies, high-dose IVIG has been used as an anti-in ammatory agent for the treatment of allergic diseases [4]. IVIG potentiates the effects of steroids by increasing steroid-binding a nity to the glucocorticoid receptor and reducing the number of circulating neutrophils by up regulating their apoptosis [5].…”

Conventional and advanced MRI evaluation of brain vascular malformations

“…This fact is of importance in selected groups of patients such as those with a history of allergy to gadolinium, patients with impaired renal function at risk for nephrogenic systemic fibrosis, and since patients with VMs will need multiple surveillance, to minimize the potential risk of intracranial gadolinium deposition. Despite no clear clinical symptoms that have been related to this deposition of gadolinium at the dentate nucleus and basal ganglia, there is a strong recommendation to justify and minimize the use of gadolinium to those circumstances where it is needed for diagnostic purposes 79,80 …”