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Longitudinal monitoring of tumor antiangiogenic therapy with near-infrared fluorophore-labeled agents targeted to integrin alpha(v)beta(3) and vascular endothelial growth factor
Sun, Xianlei1,2; Ma, Teng1,2; Liu, Hao1,2; Yu, Xinhe1,2; Wu, Yue1,2; Shi, Jiyun1,3; Jia, Bing1,2; Zhao, Huiyun1,3; Wang, Fan1,2; Liu, Zhaofei1,2
关键词Molecular Imaging Angiogenesis Avastin Arginine-glycine-aspartic Acid Tumor Response
刊名EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
2014-07-01
DOI10.1007/s00259-014-2702-1
41期:7页:1428-1439
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Radiology, Nuclear Medicine & Medical Imaging
资助者National Natural Science Foundation of China (NSFC) ; "973" projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program ; National Natural Science Foundation of China (NSFC) ; "973" projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program
研究领域[WOS]Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]F-18-FDG PET ; ANGIOGENESIS ; CANCER ; METASTASIS ; INHIBITOR ; SUNITINIB ; EFFICACY ; PEPTIDE ; CELLS ; VEGF
英文摘要

Purpose Optical imaging is emerging as a powerful tool for the noninvasive imaging of the biological processes in living subjects. This study aimed to investigate whether optical imaging of integrin alpha(v)beta(3) and vascular endothelial growth factor (VEGF) expression can serve as sensitive biomarkers for tumor early response to antiangiogenic therapy.

Methods We synthesized two near-infrared fluorescence (NIRF) imaging agents, CF680R-3PRGD2 and CF750-BevF(ab′)(2), which were designed to specifically bind to integrin alpha(v)beta(3) and VEGF, respectively. The ability of optical imaging using the two imaging agents for early monitoring the antiangiogenic effect of sunitinib was evaluated.

Results CF680R-3PRGD2 and CF750-BevF(ab′)(2) specifically bound to their respective targets in vitro and in HT-29 tumor-bearing nude mice. Sunitinib treatment led to significantly decreased tumor uptake of CF680R-3PRGD2 (e.g., 7.47 +/- 1.62 % vs. 4.24 +/- 0.16 % on day 4; P < 0.05) and CF750-BevF(ab′)(2) (e.g., 7.43 +/- 2.43 % vs. 4.04 +/- 1.39 % on day 2; P < 0.05) in vivo. Immunofluorescence staining and an enzyme-linked immunosorbent assay confirmed that sunitinib-induced changes in tumor uptake of CF680R-3PRGD2 and CF750-BevF(ab′)(2) were correlated with changes in the levels of integrin alpha(v)beta(3) and VEGF. Radiobiodistribution of Tc-99m-3PRGD2 and I-125-BevF(ab′)(2), the radiocounterparts of CF680R-3PRGD2 and CF750-BevF(ab′)(2), respectively, also validated optical imaging results.

Conclusion Longitudinal monitoring of tumor integrin alpha(v)beta(3) and VEGF expression could be used as early biomarkers for tumor response to antiangiogenic therapy. This strategy may facilitate the development of new antiangiogenic drugs, and be used for elucidation of the underlying mechanisms of therapies involving the integrin and the VEGF signaling pathway.

语种英语
所属项目编号81222019 ; 81125011 ; 81000625 ; 2013CB733802 ; 2011CB707703 ; 2011YQ030114 ; 2012ZX09102301 ; 2012BAK25B03 ; 31300 ; BMU20110263 ; 7132131 ; 7132123 ; Z121107002512010
资助者National Natural Science Foundation of China (NSFC) ; "973" projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program ; National Natural Science Foundation of China (NSFC) ; "973" projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program
WOS记录号WOS:000337286200019
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52721
专题北京大学医药卫生分析中心
作者单位1.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China
3.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China
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GB/T 7714
Sun, Xianlei,Ma, Teng,Liu, Hao,et al. Longitudinal monitoring of tumor antiangiogenic therapy with near-infrared fluorophore-labeled agents targeted to integrin alpha(v)beta(3) and vascular endothelial growth factor[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2014,41(7):1428-1439.
APA Sun, Xianlei.,Ma, Teng.,Liu, Hao.,Yu, Xinhe.,Wu, Yue.,...&Liu, Zhaofei.(2014).Longitudinal monitoring of tumor antiangiogenic therapy with near-infrared fluorophore-labeled agents targeted to integrin alpha(v)beta(3) and vascular endothelial growth factor.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,41(7),1428-1439.
MLA Sun, Xianlei,et al."Longitudinal monitoring of tumor antiangiogenic therapy with near-infrared fluorophore-labeled agents targeted to integrin alpha(v)beta(3) and vascular endothelial growth factor".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 41.7(2014):1428-1439.
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