Long term evaluation of Fe-59 labeled iron oxide nanoparticles in vivo
The Journal of Nuclear Medicine(2012)
摘要
1547 Objectives The long term evaluation of nanoparticles (NPs) in the body is a major issue, which has been raised from the recent development of nano-medicine. Most studies have been carried out in vitro cellular toxicity, and always required validation in vivo. Several kinds of iron oxide NPs have been labeled with radioisotopes to evaluate the biodistribution in vivo or to image and trace the radiolabeled iron oxide NPs in animal models. However, such kinds of image purpose radioisotopes or the surface modification labeling method could show in vivo behavior of NPs at most for a week. Here we have synthesized 59Fe labeled iron oxide core NPs and evaluated the biodistribution in vivo in mice up to a month. Methods 59Fe labeled iron oxide NPs were synthesized by thermal decomposition method and hydrophilized with PEG derivatives using ligand exchange method. Two different size of 59Fe labeled NPs were prepared and intravenously injected (0.15 uCi/0.1 mL, 12.3 mg Fe/kg) into ICR mice (25.3±1.1 g, n=4/group). Biodistribution data were obtained at 1, 2, 6 hrs and 1, 2, 4, 8, 15, 30 days after injection. Results The size of 59Fe labeled NPs was checked by particle size analyzer to be 20 or 90 nm after the hydrophilization. Both size of 59Fe labeled NPs showed similar uptake pattern and major uptake organs were liver and spleen. Blood radioactivity was decreased from 1 hr to 6 hrs and again increased after 1 day up to 30 days. Radioactivity in blood was proven to be 59Fe-hemoglobin by size exclusion HPLC with gamma detector, and this 59Fe was detached from iron oxide NP core in the liver or spleen. Conclusions We have synthesized 59Fe labeled iron oxide NPs and evaluated the biodistribution in vivo in mice up to a month. Iron oxide core radiolabeling method can be used for other iron oxide NPs and long term evaluation in vivo
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