MR cholangiography demonstrates unsuspected rapid biliary clearance of nanoparticles in rodents: implications for clinical translation.
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.
Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research and Cellular Imaging Section, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jwmbulte@mri.jhu.edu.
Jeff W M
JW
Bulte
Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.
Anne H
AH
Schmieder
Philips Research, Hamburg, Germany.
Jochen
J
Keupp
Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA; Philips Healthcare, Cleveland, OH, USA.
Shelton D
SD
Caruthers
Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.
Samuel A
SA
Wickline
Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.
Gregory M
GM
Lanza
D000818:Animals; D001659:Biliary Tract / Q000378:metabolism*; D002758:Cholangiography / Q000379:methods*; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles; D051381:Rats; D057170:Translational Research, Biomedical
D003287:Contrast Media; D019786:Gadolinium DTPA
Cholangiography; Hepatobiliary clearance; MR contrast agent; MRI; Nanoparticle; Rat