Abstract #0451

Development of Gadoxetate DCE-MRI to Evaluate Liver Transporter Function: Reproducibility of Established Technique and Application in OATP KO Rats

Apoorva Mondal¹, Xiangjun Meng², Richard Kennan³, Jocelyn Yabut⁴, Cristian Salinas⁵, and Catherine D. G. Hines²

¹Telecommunications Engineering, University of Maryland-College Park, College Park, MD, United States, ²Translational Imaging Biomarkers, Merck Research Laboratories, West Point, PA, United States, ³Translational Imaging Biomarkers, Merck Research Laboratories, Kenilworth, NJ, United States, ⁴Pharmacokinetics, Merck Research Laboratories, Rahway, NJ, United States, ⁵Biogen, Inc., Cambridge, MA, United States

Recently, Ulloa et al described a compartmental modeling approach to measure gadoxetate influx and efflux as a potential biomarker of hepatobiliary transporter function, as uptake and efflux are mediated by known transporters. The purpose of this study was to reproduce the described acquisition and post-processing, and apply the MRI assay to variations of liver influx transporter Oatp1a/1b knock-out (KO) rats to potentially differentiate between degrees of transporter function. In vivo results demonstrate significant differences in influx constants between groups of KO rats, and that this assay may be suitable for investigating drug-induced liver injury and drug-drug interactions.

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