Abstract
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Objectives: The aim of this study was to investigate the radiosensitizing effect of the 64Cu-labeled AGuIX used in the radiotherapy of HepG2 xenograft tumor model.
Methods: The HepG2 subcutaneous transplantation tumor nude mice model was established to evaluate radiosensitizing effect of the nanoparticles used in the radiotherapy. First, AGuIX nanoparticles were labeled with 64Cu at high efficiency. Tumor accumulation was accessed by ex vivo biodistribution and in vivo nano PET/MR imaging. Mice were administered via intravenous injection with 10mg of AGuIX,1mg of AGuIX and normal saline as blank control. One hour after injection, these nude mice were irradiated using an X-ray source. To evaluate the localization of 64Cu-labeled AGuIX, nano PET/MR imaging and biodistribution were performed in HepG2 tumor-bearing mice. Tumor growth was measured to evaluate the radiotherapy effect. Results: After intravenous administration of 64Cu-labeled AGuIX, The highest uptake of 64Cu-labeled AGuIX in HepG2 tumor as well as relatively low in the normal liver tissues was found at 1 hours by nano PET/MR imaging and biodistribution. Transmission electron microscope showed the nanoparticles uptake into the cytoplasm of HepG2 cells. The preliminary results suggested that the optimal time for radiotherapy with AGuIX was around 1 hours after injection of it. After 12 days the mice bearing HepG2 tumor irradiated with X-ray source, the diameter of the tumor of the mice intravenous administration of 10mg of the AGuIX were significantly smaller than those with 1mg of the AGuIX and normal saline(p< 0.05). And there was no significantly difference of the diameter of the tumor between those intravenous administration of 1mg AGuIX and normal saline. Conclusion: These results suggest that AGuIX may be potential theranostic nanoprobes for image-guided radiotherapy to enhance radiotherapy effect in HCC in vivo in the clinical setting.