Conceived and designed the experiments: YM. Performed the experiments: YM MW EN. Analyzed the data: YM. Contributed reagents/materials/ analysis tools: YM EK. Wrote the paper: YM KI EK. Histological study of the biodynamics of iron oxide nanoparticles with different diameters The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and SPIO, respectively) particles that were injected intraperitoneally into 36 C57BL/6 mice were investigated chronologically. Their distribution was studied histologically at six time points by measuring iron-positive areas (μm(2)) in organ sections stained with Prussian blue. The uptake of the differently sized particles was also compared by cultured murine macrophages (J774.1). Iron-positive areas in the liver were significantly larger in the mice injected with USPIO than those injected with SPIO at the first three time points (P < 0.05). The amount of USPIO in the lung parenchyma around the airway was larger than that of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not significantly different. The amount of iron was significantly larger in SPIO- than USPIO-treated cultured cells (P < 0.05). In conclusion, it is suggested that intra peritoneally injected USPIO particles could be used more quickly than SPIO to make Kupffer images of the liver and that both agents could help get lymph node images of similar quality. The uptake of superparamagnetic iron oxide (SPIO) particles by cells of the mononuclear phagocytic system (MPS) results in hepatic, splenic, bone marrow, and nodal iron accumulation. 1, 2 The selective accumulation of these particles by the MPS is exploited at organ-specific magnetic resonance imaging (MRI). [3] [4] [5] [6] [7] [8] [9] [10] The biodynamics of iron oxide nanoparticles vary depending on particle diameter. Unlike SPIO preparations comprised of large particles and magnetite microspheres (mean particle diameter, 72 nm and 1-5 µm, respectively), ultrasmall superparamagnetic iron oxide (USPIO) particles (mean diameter, 18 nm) are not immediately recognized by the hepatic and splenic MPS. 11, 12 The resultant prolongation of its intravascular half-life, together with its inherent T1 shortening properties, render USPIO a useful magnetic resonance angiography blood-pool agent. 13, 14 In contrast to large-particle superparamagnetic agents, the size of USPIO particles allows the extravasation of USPIO through capillary pores, the diameters of which range from 5 to 100 nm, and this capillary permeability facilitates the uptake of USPIO in MPS cells throughout the body. 15 Although information on the biodynamics of iron oxide nanoparticles of different diameters is important for various organ-specific MRI studies, to date this issue has not been addressed histologically. Therefore, a comparative histological study of the sequential biodynamics of USPIO and SPIO was performed. 