Since the first clinical use of gadopentetate other GBCAs have been commercialised for clinical use, including gadoterate meglumine, gadoteridol, gadodiamide, gadobutrol, gadobenate dimeglumine and gadoxetate (Fig. GBCAs utilise gadolinium as it creates a high magnetic moment which results in shortening of the T1 and T2 relaxation times of surrounding hydrogen protons, resulting in increased signal and improved contrast on MRI scans. Thirty tons of gadolinium metal ion were cumulatively administered to patients worldwide between 19 and this number has now exceeded 50 tons of gadolinium annually (Caravan et al. Tens of millions of contrast enhanced MRI (CE-MRI) exams are performed annually around the world. It was developed using a chelate (diethylenetriamine penta-acetic acid) to produce gadopentetate dimeglumine the first clinically available GBCA, approved for use in multiple countries in 1988 as Magnevist, with 8 more GBCAs molecules being approved for worldwide use since then (Weinmann et al. Gadolinium (Gd 3+) showed the most promising enhancement effect of the paramagnetic ions tested. Manganese, copper, chromium, ferric chloride and gadolinium-based contrast agents (GBCA) were initially used to assess the suitability of these ions as contrast agents (Runge et al. Soon after the discovery of MRI, the use of paramagnetic ions was investigated as a way of increasing the contrast and discernibility of images owing to the susceptibility of ions to external fields due to unpaired electrons (Lauterbur et al. MRI employs the use of magnetic fields to force proton spin axes to undergo longitudinal alignment and when the field is turned off the protons return to their original spin axis, releasing radio frequencies, detected by coils used to construct MR images (Lauterbur et al. Hydrogen protons are abundant in the body due to high fat and water content, and they spin with random alignment. The 1940s marked the first use of nuclear magnetic resonance (NMR) and this was subsequently adapted using the interaction of magnetic gradients to develop a whole-body magnetic resonance imaging (MRI) scanner to image the human body (Bloembergen et al. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected.
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