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Conference Abstract: DILI imaging biomarkers

Overview of the TRanslational Imaging in Drug SafeTy AssessmeNt (TRISTAN) IMI Consortium and Progress towards Standardization of MR Biomarkers of Liver Injury and Drug-Drug Interactions

Aleksandra Galetin, Claudia Green, Catherine Hines, Paul Hockings, Lisa Jarl, Gerry Kenna, Sascha Koehler, Iina Laitinen, Xiangjun Meng, Corin Miller, Kayode Ogungbenro, Geoff Parker, Ian Rowe, Gunnar Schuetz, Daniel Scotcher, Steven Sourbron, Klaus Strobel, Sirisha Tadimalla, Ekaterina Tankisheva, John Waterton, Sabina Ziemian


In Vivo MR Gordon Research Conference, 15-20 July 2018, Andover, NH, USA

 

Abstract

In 2017, the TRanslational Imaging in Drug SafeTy AssesmeNt (TRISTAN) Innovative Medicines Initiative (IMI) consortium commenced to leverage the potential of imaging techniques to improve drug safety analysis and translatability of findings by validating and making available imaging procedures as assays to provide biomarkers for widespread use. As such, hepatobiliary transporter assessment is being undertaken using gadoxetate-enhanced MRI-derived biomarkers. Gadoxetate is known to be a substrate for the human influx transporters OATP1B1, OATP1B3, and NTCP, and the efflux transporters MRP2 and MRP3, and their rat orthologues. These transporters contribute to relevant transporter-mediated drug-drug interactions and mediate hepatobiliary clearance of numerous drugs which cause drug-induced liver injury. In addition, inhibition of bile acid excretion by drugs is an important mechanism by which drug-induced liver injury can be initiated. In view of this, the authors seek to validate influx and efflux rates of gadoxetate as an imaging biomarker assay for in vivo liver transporter assessment.