Integration of gadolinium in nanostructure for contrast enhanced‐magnetic resonance imaging

Abstract

Magnetic resonance imaging (MRI) is a routinely used imaging technique in medical diagnostics, which is further enhanced with the use of contrast agents (CAs). The most commonly used CAs are gadolinium‐based contrast agents (GBCAs), in which gadolinium (Gd) is chelated with organic chelating agents (linear or cyclic). However, the use of GBCA is related to toxic side effect due to the release of free Gd3+ ions from the chelating agents. The repeated use of GBCAs has led to Gd deposition in various major organs including bone, brain, and kidneys. As a result, the use of GBCA has been linked to the development of nephrogenic systemic fibrosis (NSF). Due to the GBCA associated toxicities, some clinically approved GBCAs have been limited or revoked recently. Therefore, there is an urgent need for the development of new strategies to chelate and stabilize Gd3+ ions for contrast enhancement, safety profile, and selective imaging of a pathological site. Toward this endeavor, GBCAs have been engineered using different nanoparticulate systems to improve their stability, biocompatibility, and pharmacokinetics. Throughout this review, some of the important strategies for engineering small molecular Gd3+ chelates into a nanoconstruct is discussed. We focus on the development of GBCAs as liposomes, mesoporous silica nanoparticles (MSNs), polymeric nanocarriers, and plasmonic nanoparticles‐based design strategies to improve safety and contrast enhancement for contrast enhanced‐magnetic resonance imaging (Ce‐MRI). We also discuss the in‐vitro/in‐vivo properties of strategically designed nanoscale MRI CAs, its potentials, and limitations. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Diagnostic Tools > Diagnostic Nanodevices Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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“…Currently, the most widely used MRI CAs are gadolinium (Gd 3+ ) chelates (Marasini et al, 2020). By using high-field MRI, Gd 3+ chelates can demonstrate the Aβ plaque imaging both ex vivo and in vivo (Sillerud et al, 2013).…”

“…Due to the long electron spin-lattice relaxation time and abundant unpaired electrons (seven) per Gd 3+ ion has, the relaxation rate of water hydrogen can be increased significantly. However, ionic gadolinium complexes can leak toxic Gd 3+ ions with short half-life and it has been reported that Gd 3+ chelates can lead to renal insufficiency (Rashid et al, 2016;Marasini et al, 2020). Fluorinated small molecules that bind to amyloid plaques can be detected by 19 F MRI (Jirak et al, 2019).…”

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