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

Jeff W.M. Bulte, Anne H. Schmieder, Jochen Keupp, Shelton D. Caruthers, Samuel A. Wickline, Gregory M. Lanza

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safety and efficacy for pharmaceutical development in human disease. In this report, MR cholangiography demonstrated an unexpected rapid (<. 5. min) biliary elimination of gadolinium-perfluorocarbon nanoparticles (approximately 250. nm diameter) into the common bile duct and small intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of this dissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predicting nanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity. From the Clinical Editor: Comprehensive understanding of nanoparticle clearance is a clear prerequisite for human applications of nanomedicine-based therapeutic approaches. Through a novel use of MR cholangiography, this study demonstrates unusually rapid hepatic clearance of gadolinium-perfluorocarbon nanoparticles in rodents, in a pattern that is different than what is observed in larger animals and humans, raising awareness of important differences between common rodent-based models and larger mammals.

Original languageEnglish
Pages (from-to)1385-1388
Number of pages4
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number7
DOIs
StatePublished - Oct 1 2014

Keywords

  • Cholangiography
  • Hepatobiliary clearance
  • MR contrast agent
  • MRI
  • Nanoparticle
  • Rat

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