Abstract
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Objectives The aim of this study was to investigate the therapeutic efficacy of the combination of Lipotecan and 188Re-liposome in Huh-7 xenograft tumor model.
Methods The Huh-7 subcutaneous transplantation tumor animal model was established to evaluate the antitumor activity of 188Re-liposome combined with Lipotecan treatment compared with monotherapy. First, we investigated the maximum tolerated dose (MTD) of 188Re-liposome or Lipotecan. Mice were administered via intravenous injection with 188Re-liposome (8.65 MBq, 2/5 MTD), Lipotecan (24 mg/kg, 1/5 MTD or 48 mg/kg, 2/5 MTD) and normal saline as blank control. To evaluate the targeting and localization of 188Re-liposome, micro-autoradiography, nanoSPECT/CT imaging and biodistribution were performed in Huh-7 tumor-bearing mice. Tumor growth and body weight were measured to evaluate the antitumor effect.
Results After intravenous administration of 188Re-liposome, The highest uptake of 188Re-liposome in Huh-7 tumor was found at 24 hours by nanoSPECT/CT imaging and biodistribution. Micro-autoradiography showed dense silver grains surrounding the tumors. The preliminary results suggested that the optimal time for Lipotecan treatment was around 24 hours after injection of 188Re-liposome. The mean tumor growth inhibition rate (MGI) of Huh-7 tumors after treatment with 8.65 MBq 188Re-liposome and 48 mg/kg Lipotecan was 36% and that after treatment with 8.65 MBq 188Re-liposome and 24 mg/kg Lipotecan was 54.8%, both were significantly higher than that after treatment with the same dose of 188Re-liposome or Lipotecan alone (p < 0.05). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.356) for combination therapy.
Conclusions These results suggest that Lipotecan may be usefully integrated into the 188Re-liposome treatment of Huh-7 tumors, with potential benefits resulting from increased tumor cell radiosensitization and to assess its potential in vivo in the clinical setting.