Gadoxetate disodium, a modern hepatospecific MRI contrast agent: Indirect signs for gadolinium deposition in the brain structures with signal intensity increase after intravenous application

Holešta, Michal; Weichet, J.; Wagnerova, Monika Grilli; Lukavský, Jiřı́; Malíková, Hana

doi:10.4103/0028-3886.246259

Cited by 5 publications

(2 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, only a few studies have evaluated gadolinium deposition after the administration of GD, and the results are divergent in both clinical and animal studies. Although Conte et al [ 31 ] and Ichikawa et al [ 32 ] demonstrated that multiple administrations of GD were not associated with increased signal in dentate nucleus and globus pallidus on unenhanced T1-weighted images, subsequent reports have shown the opposite results [ 21 , 22 , 33 ]. An autopsy study by Murata et al [ 34 ] used ICP-MS and confirmed that gadolinium deposition occurred in the brain of a decedent with normal kidney function who had been administered GD.…”

Section: Discussionmentioning

confidence: 99%

“…As a linear GBCA, gadoxetate disodium (GD) can improve the detection rate and characterization of liver lesions due to its specific hepatobiliary stage imaging, which has not been suspended by the European Medicines Agency and is still widely used for liver assessment [ 21 ]. However, several clinical studies have shown increased signal intensity in dentate nucleus after GD administration, probably due to gadolinium deposition [ 21 , 22 ]. Animal experiments further confirmed gadolinium deposition in organs after the administration of GD [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium

Wei,

Hu,

et al. 2024

Heliyon

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium

Wei,

Hu,

et al. 2024

Heliyon

View full text Add to dashboard Cite

Cumulative administrations of gadolinium-based contrast agents: risks of accumulation and toxicity of linear vs macrocyclic agents

Chehabeddine

Saleh

Baalbaki

et al. 2019

Critical Reviews in Toxicology

View full text Add to dashboard Cite

Gadolinium Presence in the Brain After Administration of the Liver-Specific Gadolinium-Based Contrast Agent Gadoxetate

Jošt¹,

Frenzel²,

Boyken³

et al. 2019

Invest Radiol

View full text Add to dashboard Cite

Objective Clinical studies have reported different results regarding the signal intensity (SI) increase in the dentate nucleus on unenhanced T1-weighted magnetic resonance imaging (MRI) after repeated administrations of gadolinium-based contrast agents (GBCAs). The aim of this study was to evaluate MRI SI changes and gadolinium (Gd) brain concentrations in an animal model after repeated administration of liver-specific linear gadoxetate in comparison to multipurpose linear and macrocyclic GBCAs. Recently, it was demonstrated that small amounts of GBCAs are able to cross the blood–cerebrospinal fluid (CSF) barrier. Therefore, a secondary aim was to test if the administration of these GBCAs directly into the CSF results in a similar MRI pattern and brain Gd concentration than after systemic intravenous injection. Materials and Methods Forty-eight Han-Wistar rats were equally divided into the following 4 groups: gadoxetate (liver-specific linear), gadodiamide (multipurpose linear), gadobutrol (multipurpose macrocyclic), and control (saline, artificial CSF). For systemic application, 6 animals per group received 8 intravenous injections on 4 consecutive days per week over 2 weeks using a dose of 0.15 mmol/kg for gadoxetate and 0.6 mmol/kg for multipurpose GBCAs per injection, which corresponds to the recommended clinical dose in humans. For CSF application, 6 animals per group received one intracisternal administration of 0.31 μmol Gd (gadoxetate) and 1.25 μmol Gd (multipurpose GBCAs) or an equal volume of artificial CSF. Brain MRI was performed after a period of 5 weeks to evaluate the SI in deep cerebellar nuclei (DCN) and brain stem. Subsequently, animals were euthanized and their brains were dissected for Gd quantification by inductively coupled plasma-mass spectrometry. Results Visually evident increased SIs in the DCN were observed in blinded image review only after administration of gadodiamide. The respective SI ratios between DCN and brain stem were significantly higher compared with the control groups (P = 0.009 and P = 0.002 for intravenous and intracisternal application, respectively), whereas no difference was found for gadoxetate and gadobutrol (P ≥ 0.9). Inductively coupled plasma–mass spectrometry revealed the lowest Gd content in the brain tissue after administration for gadoxetate. The mean Gd concentrations in the cerebellum were 0.08 nmol/g (gadoxetate), 2.66 nmol/g (gadodiamide), and 0.26 nmol/g (gadobutrol) after intravenous administration, and 0.28 nmol/g (gadoxetate), 3.23 nmol/g (gadodiamide), and 0.69 nmol/g (gadobutrol) after intracisternal application. Conclusions This rat study demonstrates distinct differences in the presence of gadolinium in the brain between the liver-specific linear gadoxetate and the multipurpose linear GBCA gadodiamide. No MRI signal alterations were observed after 8 dose-adapted intravenous or a single intracisternal administrations of gadoxetate and multipurpose macrocyclic gadobutrol. The Gd concentrations in the brain 5 weeks after intravenous administration of gadoxetate were an order of magnitude lower compared with gadodiamide and slightly lower than for gadobutrol. Likely reasons for these differences are the 4-fold lower dose, the dual excretion pathway, and the higher complex stability of gadoxetate compared with multipurpose linear GBCAs. The similar findings for both routes of GBCA administration underlines the assumption that the very small amount of GBCAs that cross the blood-CSF barrier is further transported into the brain tissue.

show abstract

Gadoxetate disodium, a modern hepatospecific MRI contrast agent: Indirect signs for gadolinium deposition in the brain structures with signal intensity increase after intravenous application

Cited by 5 publications

References 1 publication

Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium

Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium

Cumulative administrations of gadolinium-based contrast agents: risks of accumulation and toxicity of linear vs macrocyclic agents

Gadolinium Presence in the Brain After Administration of the Liver-Specific Gadolinium-Based Contrast Agent Gadoxetate

Contact Info

Product

Resources

About