Gadoxetate DCE-MR imaging – exciting results on the validation of gadoxetate as a biomarker of liver function

Today, the ILSI-HESI Translational Imaging Liver project published new, exciting data in Plos-one, A multi-center preclinical study of Gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function, showing that gadoxetate DCE-MRI may be a useful tool to further understand liver function. Paul Hockings, Imaging Director at Antaros Medical and Adjunct Professor of Chalmers University of Technology, has led the working group.

This study demonstrates that gadoxetate DCE-MRI, in a multicentre setting, is a sensitive and robust biomarker to detect early changes in hepatobiliary transporter function in vivo in rats prior to established biomarkers of liver toxicity.

These results are a first step in the validation of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter function and may be of value in the evaluation of drug safety and ultimately also be of use in clinical practice for patients.

In addition, despite widespread recognition of the importance of multicenter studies in biomarker validation, to the best of the our knowledge, this study is the first in vivo multicenter preclinical imaging study. This multi-center study has shown that comparable drug effect size can be found in different laboratories when using pharmacokinetic endpoints to measure gadoxetate uptake and excretion. This result gives confidence that further consortium work to evaluate gadoxetate DCE-MRI can be reproduced between multiple laboratories. For the individual pharmaceutical companies, it gives confidence that comparable results may be obtained even if a gadoxetate DCE-MRI study is outsourced due to lack of internal resources. Results based on descriptive analysis techniques should be avoided in the multi-center setting.

The present work was conducted as part of the International Life Sciences Institute Health and Environmental Sciences Institute Translational Imaging Committee program (ILSI-HESI). This is a consortium of industry, government, and academic scientists whose mission is to advance development of biomarkers of target organ toxicity that bridge from the preclinical to the clinical stages of drug development. Participants in this consortium subgroup, which focused on liver imaging, were Amgen, AstraZeneca, FDA, GlaxoSmithKline, and The University of North Carolina at Chapel Hill.

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