title: Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging.
abstract: The purpose of this study was to determine the cellular distribution and degradation in rat liver following intravenous injection of superparamagnetic iron oxide nanoparticles used for magnetic resonance imaging (NC100150 Injection). Relaxometric and spectrophotometric methods were used to determine the concentration of the iron oxide nanoparticles and their degradation products in isolated rat liver parenchymal, endothelial and Kupffer cell fractions. An isolated cell phantom was also constructed to quantify the effect of the degradation products on the loss of MR signal in terms of decreased transverse relaxation times, T2*. The results of this study show that iron oxide nanoparticles found in the NC100150 Injection were taken up and distributed equally in both liver endothelial and Kupffer cells following a single 5 mg Fe/kg body wt. bolus injection in rats. Whereas endothelial and Kupffer cells exhibited similar rates of uptake and degradation, liver parenchymal cells did not take up the NC100150 Injection iron oxide particles. Light-microscopy methods did, however, indicate an increased iron load, presumably as ferritin/hemosiderin, within the hepatocytes 24 h post injection. The study also confirmed that compartmentalisation of ferritin/hemosiderin may cause a significant decrease in the MRI signal intensity of the liver. In conclusion, the combined results of this study imply that the prolonged presence of breakdown product in the liver may cause a prolonged imaging effect (in terms of signal loss) for a time period that significantly exceeds the half-life of NC100150 Injection iron oxide nanoparticles in liver.
authors.affiliation: Amersham Health, Nydalen 0401, PO Box 4220 Oslo, Norway. karen.briley.sabo@amersham.com
authors.forename: Karen
authors.initials: K
authors.lastname: Briley-Saebo
authors.forename: Atle
authors.initials: A
authors.lastname: Bjørnerud
authors.forename: Derek
authors.initials: D
authors.lastname: Grant
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlstrom
authors.forename: Trond
authors.initials: T
authors.lastname: Berg
authors.forename: Grete Mørk
authors.initials: GM
authors.lastname: Kindberg
mesh_terms: D000818:Animals; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D003287:Contrast Media / Q000378:metabolism* / Q000493:pharmacokinetics*; D003911:Dextrans; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D052203:Ferrosoferric Oxide; D006485:Hemosiderin / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010087:Oxides / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D005293:Ferritins; D006485:Hemosiderin; D007501:Iron; D052203:Ferrosoferric Oxide