Short Communication MR cholangiography demonstrates unsuspected rapid biliary clearance of nanoparticles in rodents: Implications for clinical translation

AbstractDue to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safetyand efficacy for pharmaceutical development in human disease. In this report, MR cholangiography demonstrated an unexpected rapid(b5 min) biliary elimination of gadolinium–perfluorocarbon nanoparticles (approximately 250 nm diameter) into the common bile duct andsmall intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of thisdissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predictingnanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity.From the Clinical Editor: Comprehensive understanding of nanoparticle clearance is a clear prerequisite for human applications ofnanomedicine-based therapeutic approaches. Through a novel use of MR cholangiography, this study demonstrates unusually rapid hepaticclearance of gadolinium-perfluorocarbon nanoparticles in rodents, in a pattern that is different than what is observed in larger animals andhumans, raising awareness of important differences between common rodent-based models and larger mammals.© 2014 Elsevier Inc. All rights reserved.