ArticlePloS one2018
A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacokinetic Modeling of Hepatospecific MRI Contrast Agent Flux in Large Animal Models by Dynamic Contrast-Enhanced MRI.Molecular imaging and biology · 2026Article
- Pharmacokinetic modeling of hepatospecific MRI contrast agent flux in large animal models by dynamic contrast-enhanced MRI.Research square · 2026Article
- Go Fish! Hepatic Uptake of Clinical Hepatospecific Gadolinium-Based MRI Contrast Agents in Zebrafish is Similar to Humans.Molecular imaging and biology · 2025Article
- Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study.Magma (New York, N.Y.) · 2024Article
- Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.Pharmaceutics · 2023Article
- Article
- Emerging technologies and their impact on regulatory science.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats.Molecular pharmaceutics · 2021Article
- Recent Progress in the Molecular Imaging of Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Review
- Ex vivo gadoxetate relaxivities in rat liver tissue and blood at five magnetic field strengths from 1.41 to 7 T.NMR in biomedicine · 2021Article
- Use of imaging to assess the activity of hepatic transporters.Expert opinion on drug metabolism & toxicology · 2020Review
- Repeatability and reproducibility of longitudinal relaxation rate in 12 small-animal MRI systems.Magnetic resonance imaging · 2019Article
- Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort.PLoS computational biology · 2019Article
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Authors and funding
15 authors at 10 institutions in 6 countries.
Funding
Abstract
Drug-induced liver injury (DILI) is a leading cause of acute liver failure and transplantation. DILI can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s-1 (n = 23) and 11.7 +/- 1.3 s-1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s-1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s-1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic.
conclusionRate constants of gadoxetate uptake and excretion are sensitive and robust biomarkers to detect early changes in hepatobiliary transporter function in vivo in rats prior to established biomarkers of liver toxicity.
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