title: Tumor vascular homing endgolin-targeted radioimmunotherapy in hepatocellular carcinoma.
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 (131)I-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 (131)I-A8 markedly inhibits HUVECs to form extensive and enclosed tube networks. The results showed that the radiochemical purity of (131)I-A8 was 92.8 % and (131)I-A8 maintained more stable in serum than in saline and had high affinity against SMMC7721-GFP cells. The pharmacokinetics of (131)I-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 (131)I-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 (131)I-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.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Jinan, China.
authors.forename: Chong-Ling
authors.initials: CL
authors.lastname: Duan
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Hou
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Liang
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.forename: Jian-Kui
authors.initials: JK
authors.lastname: Han
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004195:Disease Models, Animal; D000071063:Endoglin; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000532:radiotherapy; D016499:Radioimmunotherapy; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface