Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats.

Physiologically based pharmacokinetic (PBPK) models are increasingly used in drug development to simulate changes in both systemic and tissue exposures that arise as a result of changes in enzyme and/or transporter activity. Verification of these model-based simulations of tissue exposure is challenging in the case of transporter-mediated drug-drug interactions (tDDI), in particular as these may lead to differential effects on substrate exposure in plasma and tissues/organs of interest. Gadoxetate, a promising magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 (OATP1B1) and multidrug resistance-associated protein 2 (MRP2).

Ex vivo gadoxetate relaxivities in rat liver tissue and blood at five magnetic field strengths from 1.41 to 7 T.

Quantitative mapping of gadoxetate uptake and excretion rates in liver cells has shown potential to significantly improve the management of chronic liver disease and liver cancer. Unfortunately, technical and clinical validation of the technique is currently hampered by the lack of data on gadoxetate relaxivity. The aim of this study was to fill this gap by measuring gadoxetate relaxivity in liver tissue, which approximates hepatocytes, in blood, urine and bile at magnetic field strengths of 1.

Optimization of Iron Oxide Tracer Synthesis for Magnetic Particle Imaging.

The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based synthesis of multicore superparamagnetic iron oxide nanoparticles stabilized with dextran (MC-SPIONs). We also demonstrate the preparation of single core superparamagnetic iron oxide nanoparticles in organic media, subsequently coated with a poly(ethylene glycol) gallic acid polymer and phase transferred to water (SC-SPIONs).