title: Quantitative evaluation of the reticuloendothelial system function with dynamic MRI.
abstract: OBJECTIVE
  To evaluate the reticuloendothelial system (RES) function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO) using dynamic magnetic resonance imaging (MRI) with two-compartment pharmacokinetic modeling.
  
  
  METHODS
  Kinetics of blood clearance and hepatic accumulation were recorded in young adult male 01b74 athymic nude mice by dynamic T2* weighted MRI after the injection of different doses of SPIO nanoparticles (0.5, 3 or 10 mg Fe/kg). Association parameter, Kin, dissociation parameter, Kout, and elimination constant, Ke, derived from dynamic data with two-compartment model, were used to describe active binding to Kupffer cells and extrahepatic clearance. The clodrosome and liposome were utilized to deplete macrophages and block the RES function to evaluate the capability of the kinetic parameters for investigation of macrophage function and density.
  
  
  RESULTS
  The two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.27±0.03). A lower Kin, a lower Kout and a lower Ke were found after clodrosome treatment, whereas a lower Kin, a higher Kout and a lower Ke were observed after liposome treatment in comparison to saline treatment (P<0.005).
  
  
  CONCLUSIONS
  Dynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hoon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D003911:Dextrans / Q000097:blood / Q000493:pharmacokinetics; D005295:Ferrocyanides / Q000378:metabolism; D007501:Iron; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D008819:Mice, Nude; D012157:Mononuclear Phagocyte System / Q000502:physiology*; D053758:Nanoparticles / Q000737:chemistry; D013154:Spleen / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003911:Dextrans; D005295:Ferrocyanides; D007501:Iron; D058185:Magnetite Nanoparticles; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C065507:ferumoxides; C000170:ferric ferrocyanide
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