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Tumor vascular homing endgolin-targeted radioimmunotherapy in hepatocellular carcinoma

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Tumor Biology

Abstract

Endoglin is a proliferation-associated cell membrane antigen and overexpressed in the angiogenic vasculature of solid tumors. However, the applications of endoglin (ENG)-targeted radioimmunotheray in hepatocellular carcinoma have not been reported yet. Therefore, the aim of this study was the visualization of both the development of hepatocellular carcinoma (HCC) tumor burden and therapeutic effect with ENG-targeted 131I-anti-ENG mAb (A8), via in vivo noninvasive fluorescence imaging (NIFLI) of SMMC7721-green fluorescent protein (GFP) cells. A8 showed a dose-dependent, time-dependent suppression on the proliferation of SMMC7721-GFP cells and human umbilical vein endothelial cells (HUVECs) in vitro. Tube formation assay showed that 131I-A8 markedly inhibits HUVECs to form extensive and enclosed tube networks. The results showed that the radiochemical purity of 131I-A8 was 92.8 % and 131I-A8 maintained more stable in serum than in saline and had high affinity against SMMC7721-GFP cells. The pharmacokinetics of 131I-A8 was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. NIFLI exhibited a good relation between the fluorescent signal and tumor volume in vivo. Furthermore, treatment with 131I-A8 resulted in significant tumor-growth suppression on the basis of the reducing fluorescent signal and a remarkably decreased tumor weight in treated animals. These results were further verified by RT-PCR and immunohistochemistry staining. Our findings indicate that 131I-A8 can be used as ENG-targeted therapy for hepatocellular carcinoma, and noninvasive fluorescence imaging provides valuable information on tumor burden and effectiveness of therapy.

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Acknowledgments

This study was supported by the Natural Science Foundation of Shandong Province (No. Y2007C088), the China Postdoctoral Science Foundation (No. 20090461227), and the Science and Technology Project of Shandong, China (2013GSF11843).

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Authors and Affiliations

  1. Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Jinan, China

    Chong-Ling Duan, Gui-Hua Hou, Yan-Ping Liu, Ting Liang, Jing Song, Jian-Kui Han & Chao Zhang

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  1. Chong-Ling Duan
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  2. Gui-Hua Hou
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Correspondence to Chao Zhang.

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Duan, CL., Hou, GH., Liu, YP. et al. Tumor vascular homing endgolin-targeted radioimmunotherapy in hepatocellular carcinoma. Tumor Biol. 35, 12205–12215 (2014). https://doi.org/10.1007/s13277-014-2529-1

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