Abstract
PurposeTo 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.Materials and MethodsKinetics 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.ResultsThe 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).ConclusionDynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level.
Highlights
The reticuloendothelial system (RES) plays an important role in inflammatory responses, antigen presentation, and immunoregulatory networks [1,2], depression of its function is likely to weaken the host defense
The two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.2760.03)
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)
Summary
The reticuloendothelial system (RES) plays an important role in inflammatory responses, antigen presentation, and immunoregulatory networks [1,2], depression of its function is likely to weaken the host defense. Bloodstream clearance of radiolabelled particles has been used to measure the function of the reticuloendothelial system [7,8,9,10]. This technique involves injecting a dose of radiolabelled particles intravenously, withdrawing venous blood samples at time intervals and calculating the clearance rate from the measurement of the radioactivity of each sample. This approach is invasive, involving exposure of the subjects to radiation, and is unlikely to be implied in the clinic. A more efficient, accurate, and safe modality needs to be developed for measurement of the reticuloendothelial phagocytic capacity
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