title: Evaluation of (188)Re-labeled NGR-VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts.
abstract: Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic protein, which includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. The NGR (asparagine-glycine-arginine)-containing peptides can specifically bind to CD13 (Aminopeptidase N) receptor which is overexpressed in angiogenic blood vessels and tumor cells. In this study, a novel NGR-VEGI fusion protein was prepared and labeled with (188)Re for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Single photon emission computerized tomography (SPECT) imaging results revealed that (188)Re-NGR-VEGI exhibits good tumor-to-background contrast in CD13-positive HT-1080 tumor xenografts. The CD13 specificity of (188)Re-NGR-VEGI was further verified by significant reduction of tumor uptake in HT-1080 tumor xenografts with co-injection of the non-radiolabeled NGR-VEGI protein. The biodistribution results demonstrated good tumor-to-muscle ratio (4.98 ± 0.25) of (188)Re-NGR-VEGI at 24 h, which is consistent with the results from SPECT imaging. For radiotherapy, 18.5 MBq of (188)Re-NGR-VEGI showed excellent tumor inhibition effect in HT-1080 tumor xenografts with no observable toxicity, which was confirmed by the tumor size change and hematoxylin and eosin (H&E) staining of major mouse organs. In conclusion, these data demonstrated that (188)Re-NGR-VEGI has the potential as a theranostic agent for CD13-targeted tumor imaging and therapy.
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi, 710032, China.|Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC 103, Los Angeles, CA, 90033-9061, USA.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi, 710032, China.|Department of Nuclear Medicine, General Hospital of Jinan Military Region, Jinan, Shandong, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Guiyu
authors.initials: G
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi, 710032, China.
authors.forename: Mingru
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Changjing
authors.initials: C
authors.lastname: Zuo
authors.affiliation: Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC 103, Los Angeles, CA, 90033-9061, USA. chenkai@med.usc.edu.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi, 710032, China. wangjing@fmmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005354:Fibrosarcoma / Q000532:radiotherapy*; D064593:Heterografts / Q000378:metabolism; D006801:Humans; D007554:Isotopes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000070816:Nogo Receptor 1 / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011877:Radionuclide Imaging / Q000379:methods; D012211:Rhenium / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000378:metabolism*
chemical_list: D007554:Isotopes; D000070816:Nogo Receptor 1; D010455:Peptides; C486580:RTN4R protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D012211:Rhenium; D018826:CD13 Antigens
keywords: CD13; Imaging; Re-188; Therapy; Vascular endothelial growth inhibitor