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Archives of Toxicology Feb 2022Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical... (Review)
Review
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. 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. 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. 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. 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.
Topics: Animals; Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging; Nephrogenic Fibrosing Dermopathy; Renal Insufficiency
PubMed: 34997254
DOI: 10.1007/s00204-021-03189-8 -
AJNR. American Journal of Neuroradiology Jan 2016
Topics: Cerebellar Nuclei; Contrast Media; Cranial Irradiation; Female; Gadolinium; Humans; Image Enhancement; Magnetic Resonance Imaging; Male
PubMed: 26494696
DOI: 10.3174/ajnr.A4608 -
European Journal of Medicinal Chemistry Aug 2022Metallofullerenols (MFs) are functionalized endohedral fullerenes connecting at least three levels of organization of matter: atomic, molecular, and supramolecular,... (Review)
Review
Metallofullerenols (MFs) are functionalized endohedral fullerenes connecting at least three levels of organization of matter: atomic, molecular, and supramolecular, resulting in their unique activity at the nanoscale. Biomedical applications of MFs started from gadolinium-containing contrasting agents, but today their potential medical applications go far beyond diagnostics and magnetic resonance imaging. In many cases, preclinical studies have shown a great therapeutic value of MFs, and here we provide an overview of interactions of MFs with high-energy radiation and with reactive oxygen species generated during radiation as a ground for potential applications in modern therapy of cancer patients. We also present the current knowledge on interactions of MFs with proteins and with other components of cells and tissues. Due to their antioxidant properties, as well as their ability to regulate the expression of genes involved in apoptosis, angiogenesis, and stimulation of the immune response, MFs can contribute to inhibition of tumor growth and protection of normal cells. MFs with enclosed gadolinium act as inhibitors of tumor growth in targeted therapy along with imaging techniques, but we hope that the data gathered in this review will help to accelerate further progress in the implementation of MFs, also the ones containing rare earth metals other than gadolinium, in a broad range of bioapplications covering not only diagnostics and bioimaging but also radiation therapy and cancer treatment by not-cytotoxic agents.
Topics: Contrast Media; Fullerenes; Gadolinium; Humans; Magnetic Resonance Imaging; Neoplasms
PubMed: 35665690
DOI: 10.1016/j.ejmech.2022.114481 -
Journal of Cerebral Blood Flow and... Feb 2021AHA guidelines recommend use of perfusion imaging for patient selection in the 6-24 h window. Recently, the safety of gadolinium-based contrast agents for MR perfusion...
AHA guidelines recommend use of perfusion imaging for patient selection in the 6-24 h window. Recently, the safety of gadolinium-based contrast agents for MR perfusion imaging has been questioned based on findings that gadolinium accumulates in brain tissue. Regulatory bodies have recommended to limit the use of gadolinium-based contrast agents where possible. Focusing specifically on the time to maximum of the tissue residue function (Tmax) parameter, used in DAWN and DEFUSE 3, we hypothesized that half-dose scans would yield a similar Tmax delay pattern to full-dose scans. We prospectively recruited 10 acute ischemic stroke patients imaged with two perfusion scans at their follow-up visit, one with a standard dose gadolinium followed by a half-dose injection a median of 7 min apart. The brain was parcellated into a grid of 3 × 3 regions and the mean of the difference in Tmax between the 3 × 3 regions on the half- and full-dose Tmax maps was 0.1 s (iqr 0.38 s). The fraction of brain tissue that differed by no more than ±1 s was 93.7%. In patients with normal or modest Tmax delays, half-dose gadolinium appears to provide comparable Tmax measurements to those of full-dose scans.
Topics: Contrast Media; Female; Gadolinium; Humans; Magnetic Resonance Imaging; Male; Perfusion Imaging; Stroke
PubMed: 32208802
DOI: 10.1177/0271678X20914537 -
Journal of Hazardous Materials Sep 2023The biosorption and recovery of ionic gadolinium (Gd) from contaminated water by the free-floating duckweed Lemna gibba was studied. The highest non-toxic concentration...
The biosorption and recovery of ionic gadolinium (Gd) from contaminated water by the free-floating duckweed Lemna gibba was studied. The highest non-toxic concentration range was determined as (6.7 mg L). The concentration of Gd in the medium and in the plant biomass was monitored and a mass balance was established. Tissue Gd concentration of Lemna increased with increasing Gd concentration of the medium. The bioconcentration factor was up to 1134 and in nontoxic concentrations up to 2.5 g kg Gd tissue concentration was reached. Lemna ash contained 23.2 g Gd kg. Gd removal efficiency from the medium was 95%, however, only 17-37% of the initial Gd content of the medium accumulated in Lemna biomass, an average of 5% remained in the water, and 60-79% was calculated as a precipitate. Gadolinium-exposed Lemna plants released ionic Gd into the nutrient solution when they were transferred to a Gd-free medium. The experimental results revealed that in constructed wetlands, L. gibba is able to remove ionic Gd from the water and can be suitable for bioremediation and recovery purposes.
Topics: Water Pollutants, Chemical; Biodegradation, Environmental; Gadolinium; Biomass; Araceae
PubMed: 37390689
DOI: 10.1016/j.jhazmat.2023.131930 -
International Journal of Molecular... Apr 2024Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment... (Review)
Review
Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment monitoring across multiple clinical settings. Studies have shown that exposure to GBCAs is associated with gadolinium release and tissue deposition that may cause short- and long-term toxicity in several organs, including the kidney, the main excretion organ of most GBCAs. Considering the increasing prevalence of chronic kidney disease worldwide and that most of the complications following GBCA exposure are associated with renal dysfunction, the mechanisms underlying GBCA toxicity, especially renal toxicity, are particularly important. A better understanding of the gadolinium mechanisms of toxicity may contribute to clarify the safety and/or potential risks associated with the use of GBCAs. In this work, a review of the recent literature concerning gadolinium and GBCA mechanisms of toxicity was performed.
Topics: Contrast Media; Gadolinium; Kidney; Body Fluids; Magnetic Resonance Imaging
PubMed: 38612881
DOI: 10.3390/ijms25074071 -
Journal of Cellular and Molecular... Apr 2020Gadolinium-containing carbon nanomaterials are a new class of contrast agent for magnetic resonance imaging. They are characterized by a superior proton relaxivity to... (Review)
Review
Gadolinium-containing carbon nanomaterials are a new class of contrast agent for magnetic resonance imaging. They are characterized by a superior proton relaxivity to any current commercial gadolinium contrast agent and offer the possibility to design multifunctional contrasts. Intense efforts have been made to develop these nanomaterials because of their potential for better results than the available gadolinium contrast agents. The aim of the present work is to provide a review of the advances in research on gadolinium-containing carbon nanomaterials and their advantages over conventional gadolinium contrast agents. Due to their enhanced proton relaxivity, they can provide a reliable imaging contrast for cells, tissues or organs with much smaller doses than currently used in clinical practice, thus leading to reduced toxicity (as shown by cytotoxicity and biodistribution studies). Their active targeting capability allows for improved MRI of molecular or cellular targets, overcoming the limited labelling capability of available contrast agents (restricted to physiological irregularities during pathological conditions). Their potential of multifunctionality encompasses multimodal imaging and the combination of imaging and therapy.
Topics: Carbon; Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Nanostructures; Tissue Distribution
PubMed: 32154648
DOI: 10.1111/jcmm.15065 -
Biometals : An International Journal on... Jun 2016Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been... (Review)
Review
Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.
Topics: Contrast Media; Gadolinium; Humans
PubMed: 27053146
DOI: 10.1007/s10534-016-9931-7 -
Molecules (Basel, Switzerland) Dec 2020Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in... (Review)
Review
Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data shows that metal may accumulate in the human body and its deposition has been detected in organs such as brain and liver. Moreover, the disease nephrogenic systemic fibrosis has been linked to increased Gd levels. Investigation of Gd effects at the cellular and molecular levels mostly revolves around calcium-dependent proteins, since Gd competes with calcium due to their similar size; other reports focus on interaction of Gd with nucleic acids and carbohydrates. However, little is known about Gd effects on membranes; yet some results suggest that Gd interacts strongly with biologically-relevant lipids (e.g., brain membrane constituents) and causes serious structural changes including enhanced membrane rigidity and propensity for lipid fusion and aggregation at much lower concentrations than other ions, both toxic and essential. This review surveys the impact of the anthropogenic use of Gd emphasizing health risks and discussing debilitating effects of Gd on cell membrane organization that may lead to deleterious health consequences.
Topics: Cell Membrane; Chelating Agents; Contrast Media; Environment; Environmental Exposure; Environmental Restoration and Remediation; Gadolinium; Health Impact Assessment; Humans; Magnetic Resonance Imaging; Models, Theoretical; Structure-Activity Relationship
PubMed: 33297578
DOI: 10.3390/molecules25235762 -
American Journal of Physiology. Renal... Jul 2016Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare... (Review)
Review
Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis.
Topics: Contrast Media; Fibrosis; Gadolinium; Humans; Magnetic Resonance Imaging
PubMed: 27147669
DOI: 10.1152/ajprenal.00166.2016