Gadolinium Deposition in Neurology Clinical Practice

Smith, Tyler; Steven, Andrew; Bagert, Bridget

doi:10.31486/toj.18.0111

Cited by 21 publications

(23 citation statements)

References 48 publications

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“…We will focus on the first five of these questions (1–5). So far, there is no clinical evidence of harmful consequences of intracerebral Gd deposition 7,17 …”

Section: International Nonproprietary Name Gadopiclenol Gadoterate Gamentioning

confidence: 99%

“…It rapidly became apparent that the gradual appearance of a T 1 hypersignal in specific structures of the CNS was almost exclusively associated with prior administrations of linear GBCAs. 16,17 This finding, associated with the previous causal relationship of nephrogenic systemic fibrosis with linear GBCAs, 18 in patients with severe renal failure prompted the European Medicines Agency to suspend the marketing authorizations for intravenous linear products. 19 Subsequently, the US Food and Drug Administration (FDA), while maintaining the authorization for linear GBCAs, recognized that these agents resulted in more brain retention than macrocyclics.…”

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confidence: 99%

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Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Rasschaert

Weller

Schroeder

et al. 2020

Magnetic Resonance Imaging

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The unexpected appearance of T1 hyperintensities, mostly in the dentate nucleus and the globus pallidus, during nonenhanced MRI was reported in 2014. This effect is associated with prior repeated administrations of gadolinium (Gd)‐based contrast agents (GBCAs) in patients with a functional blood–brain barrier (BBB). It is widely assumed that GBCAs do not cross the intact BBB, but the observation of these hypersignals raises questions regarding this assumption. This review critically discusses the mechanisms of Gd accumulation in the brain with regard to access pathways, Gd species, tissue distribution, and subcellular location. We propose the hypothesis that there is early access of Gd species to cerebrospinal fluid, followed by passive diffusion into the brain parenchyma close to the cerebral ventricles. When accessing areas rich in endogenous metals or phosphorus, the less kinetically stable GBCAs would dissociate, and Gd would bind to endogenous macromolecules, and/or precipitate within the brain tissue. It is also proposed that Gd species enter the brain parenchyma along penetrating cortical arteries in periarterial pial‐glial basement membranes and leave the brain along intramural peri‐arterial drainage (IPAD) pathways. Lastly, Gd/GBCAs may access the brain parenchyma directly from the blood through the BBB in the walls of capillaries. It is crucial to distinguish between the physiological distribution and drainage pathways for GBCAs and the possible dissociation of less thermodynamically/kinetically stable GBCAs that lead to long‐term Gd deposition in the brain. Level of Evidence 5. Technical Efficacy Stage 3.

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“…We will focus on the first five of these questions (1–5). So far, there is no clinical evidence of harmful consequences of intracerebral Gd deposition 7,17 …”

Section: International Nonproprietary Name Gadopiclenol Gadoterate Gamentioning

confidence: 99%

mentioning

confidence: 99%

Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Rasschaert

Weller

Schroeder

et al. 2020

Magnetic Resonance Imaging

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“…Currently, marketed clinical magnetic resonance contrast agents are Gd chelates. It has recently been observed in humans and preclinical models that low levels of Gd can be detected in tissue, particularly in the central nervous system following administration of multiple doses of gadoliniumbased contrast agents (GBCA) [2][3][4]. While adverse health outcomes have not been associated with this retention, the observation has revived interest in MRI active chelates of biotic metals; candidates include manganese [5,6] and iron [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging

Bales

Grimmond

Johnson

et al. 2019

Contrast Media & Molecular Imaging

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Contrast-enhanced magnetic resonance imaging is an essential tool for disease diagnosis and management; all marketed clinical magnetic resonance imaging (MRI) contrast agents (CAs) are gadolinium (Gd) chelates and most are extracellular fluid (ECF) agents. After intravenous injection, these agents rapidly distribute to the extracellular space and are also characterized by low serum protein binding and predominant renal clearance. Gd is an abiotic element with no biological recycling processes; low levels of Gd have been detected in the central nervous system and bone long after administration. These observations have prompted interest in the development of new MRI contrast agents based on biotic elements such as iron (Fe); Fe-HBED (HBED = N,N′-bis(2-hydroxyphenyl)ethylenediamine-N,N′-diacetic acid), a coordinatively saturated iron chelate, is an attractive MRI CA platform suitable for modification to adjust relaxivity and biodistribution. Compared to the parent Fe-HBED, the Fe-HBED analogs reported here have lower serum protein binding and higher relaxivity as well as lower relative liver enhancement in mice, comparable to that of a representative gadolinium-based contrast agent (GBCA). Fe-HBED analogs are therefore a promising class of non-Gd ECF MRI CA.

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“…Auch in weiteren Studien konnte bislang keine eindeutige Korrelation von Gadolinium-Retention und klinischen bzw. neurologischen Korrelaten gefunden werden [53][54][55][56].…”

Section: Gadolinium-retention Im Gehirnunclassified

Gadolinium-based contrast agents: What we learned from acute adverse events, nephrogenic systemic fibrosis and brain retention

Bäuerle¹,

Saake²,

Uder³

2020

Rofo

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Background Radiologists have been administering gadolinium-based contrast agents (GBCA) in magnetic resonance imaging for several decades, so that there is abundant experience with these agents regarding allergic-like reactions, nephrogenic systemic fibrosis (NSF) and gadolinium retention in the brain. Methods This review is based on a selective literature search and reflects the current state of research on acute adverse effects of GBCA, NSF and brain retention of gadolinium. Results Due to the frequent use of GBCA, data on adverse effects of these compounds are available in large collectives. Allergic-like reactions occurred rarely, whereas severe acute reactions were very rarely observed. Systemic changes in NSF also occur very rarely, although measures to avoid NSF resulted in a significantly reduced incidence of NSF. Due to gadolinium retention in the body after administration of linear MR contrast agents, only macrocyclic preparations are currently used with few exceptions. Clear clinical correlates of gadolinium retention in the brain could not be identified so far. Although the clinical added value of GBCA is undisputed, individual risks associated with the injection of GBCA should be identified and the use of non-contrast enhanced MR techniques should be considered. Alternative contrast agents such as iron oxide nanoparticles are not clinically approved, but are currently undergoing clinical trials. Conclusion GBCA have a very good risk profile with a low rate of adverse effects or systemic manifestations such as NSF. Gadolinium retention in the brain can be minimized by the use of macrocyclic GBCA, although clear clinical correlates due to gadolinium retention in the brain following administration of linear GBCA could not be identified yet. Key Points: Citation Format

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Gadolinium Deposition in Neurology Clinical Practice

Cited by 21 publications

References 48 publications

Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Fe-HBED Analogs: A Promising Class of Iron-Chelate Contrast Agents for Magnetic Resonance Imaging

Gadolinium-based contrast agents: What we learned from acute adverse events, nephrogenic systemic fibrosis and brain retention

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