Drug development is an expensive and resource-consuming process with a high risk of failure. Drug safety concerns are sometimes not discovered until late in development, which, in addition to putting patients at risk, can be costly and have lasting consequences for future development.
Imaging biomarkers from techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) have the potential to non-invasively offer early insights into toxicity and harmful effects, reducing drug safety risk later in development. The goal of the Translational Imaging in Drug Safety Assessment (TRISTAN) project is to validate the use of imaging biomarkers to understand, assess, and predict the toxicity and harmful effects of potential treatments early in the drug development process. Antaros Medical is proud to be part of the TRISTAN consortium.
Part of this work involves research into using dynamic contrast-enhanced MRI (DCE-MRI) with gadoxetate to understand harmful changes in hepatobiliary transporter flux that may lead to drug-induced liver injury (DILI) or adversely impact drug-drug interactions (DDI). Gadoxetic acid (gadoxetate) is a magnetic resonance (MR) contrast agent that is actively taken up by hepatocytes and excreted via the biliary system. You can read more about Antaros Medical’s work with gadoxetate-enhanced MRI here.
As both gadoxetate and the potential treatments in development are substrates of the transporters, DCE-MRI with gadoxetate can be used to measure transporter inhibition or alteration, providing information that can be used to predict the risk of DILI or DDI. However, reproducibility is a challenge that currently limits the utility of DCE-MRI biomarkers in both preclinical and clinical testing. The aim of this work was to understand and improve the previously reported variability in DCE-MRI biomarkers of hepatocellular function in rats.
A reproducibility study was initiated to investigate the sources of between-centre variability to inform method development and guide clinical trials. The results from this study were recently published in Magnetic Resonance Materials in Physics Biology and Medicine (MAGMA).
TRISTAN
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116106. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
For more information about TRISTAN, please check the IMI website, the TRISTAN website, or the IMI Project factsheet.
Find the publication details below
Title: Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study
Authors: Gunwhy ER, Hines CDG, Green C, Laitinen I, Tadimalla S, Hockings PD, Schütz G, Kenna JG, Sourbron S, Waterton JC
Find the publication link here.