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学科主题基础医学
Specific Targeting of Human Integrin alpha(v)beta(3) with In-111-Labeled Abegrin (TM) in Nude Mouse Models
Liu, Zhaofei1,2; Jia, Bing1,2; Zhao, Huiyun1,2; Chen, Xiaoyuan3,4; Wang, Fan1,2
关键词Tumor Integrin alpha(v)beta(3) In-111 Abegrin (TM) Imaging
刊名MOLECULAR IMAGING AND BIOLOGY
2011-02-01
DOI10.1007/s11307-010-0302-4
13期:1页:112-120
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Radiology, Nuclear Medicine & Medical Imaging
研究领域[WOS]Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]POSITRON-EMISSION-TOMOGRAPHY ; RGD-BOMBESIN HETERODIMER ; MONOCLONAL-ANTIBODY LA22 ; IN-VITRO ; CANCER-THERAPY ; TUMOR ; RECEPTOR ; ALPHA-V-BETA-3 ; EXPRESSION ; ANGIOGENESIS
英文摘要

The cell adhesion molecule integrin alpha(v)beta(3) is an important player in the process of tumor angiogenesis and metastasis. Abegrin (TM), a fully humanized anti-integrin alpha(v)beta(3) monoclonal antibody, was currently in clinical trials for cancer therapy. Herein, we labeled Abegrin (TM) with In-111, evaluated the in vitro and in vivo characteristics, and investigated whether the expression of integrin alpha(v)beta(3) in tumors could be imaged with In-111-labeled Abegrin (TM).

The binding affinity and specificity of Abegrin (TM) was analyzed using U87MG glioblastoma cells. Abegrin (TM) was coupled with 1,4,7,10-tetraazadodecane-N,N′,NaEuro(3),N′aEuro(3)-tetraacetic acid (DOTA) for In-111 radiolabeling. gamma Imaging of In-111-DOTA-Abegrin (TM) was carried out in nude mice bearing both integrin alpha(v)beta(3)-positive U87MG and integrin alpha(v)beta(3)-negative HT-29 tumors. Biodistribution and blocking studies of In-111-DOTA-Abegrin (TM) were investigated in U87MG tumor-bearing nude mice.

Abegrin (TM) exhibited high-binding affinity to human integrin alpha(v)beta(3) expressed on U87MG cells (K (d) of 0.35 +/- 0.06 nM). The antibody retained antigen-binding affinity/specificity after DOTA conjugation. gamma Imaging showed that the tumor uptake of In-111-DOTA-Abegrin (TM) in integrin alpha(v)beta(3)-positive U87MG tumors was much higher than that in integrin alpha(v)beta(3)-negative HT-29 tumors. In the HT-29 tumors, Abegrin (TM) was mainly nonspecifically accumulated around the blood vessels, while in the U87MG tumors, besides the nonspecific tumor retention, Abegrin (TM) also specifically bound the human integrin alpha(v)beta(3) expressed on the tumor cells. Biodistribution and blocking studies exhibited that the U87MG tumor uptake of In-111-DOTA-Abegrin (TM) decreased from 14.12 +/- 0.44 to 6.93 +/- 0.94 percentage of injected dose per gram of tissue after coinjection of excess dose of cold Abegrin (TM), which confirmed the in vivo integrin alpha(v)beta(3) binding specificity of In-111-DOTA-Abegrin (TM).

Abegrin (TM) showed specific binding to human integrin alpha(v)beta(3) expressed on the tumor cells. In-111-DOTA-Abegrin (TM) can specifically target the human integrin alpha(v)beta(3) expression in the nude mouse model. In-111-DOTA-Abegrin (TM) has a potential for clinical translation as an agent for integrin alpha(v)beta(3)-positive tumor imaging, evaluating tumor angiogenic status and monitoring the therapeutic efficacy of Abegrin (TM)-based cancer therapy.

语种英语
WOS记录号WOS:000286395600015
项目编号30930030 ; 30870728 ; 30900373 ; 20820102035 ; 2007AA02Z467 ; 2009ZX09103-733 ; 2009ZX09301-010 ; 2009ZX09103-746
资助机构NSFC ; 863 project ; Ministry of Science and Technology of China
引用统计
被引频次:14[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/400002259/60029
专题北京大学基础医学院
作者单位1.Peking Univ, Sch Basic Med Sci, 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.Stanford Univ, Sch Med, MIPS, Dept Radiol,Biophys & Biox Program, Stanford, CA 94305 USA
4.NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA
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GB/T 7714
Liu, Zhaofei,Jia, Bing,Zhao, Huiyun,et al. Specific Targeting of Human Integrin alpha(v)beta(3) with In-111-Labeled Abegrin (TM) in Nude Mouse Models[J]. MOLECULAR IMAGING AND BIOLOGY,2011,13(1):112-120.
APA Liu, Zhaofei,Jia, Bing,Zhao, Huiyun,Chen, Xiaoyuan,&Wang, Fan.(2011).Specific Targeting of Human Integrin alpha(v)beta(3) with In-111-Labeled Abegrin (TM) in Nude Mouse Models.MOLECULAR IMAGING AND BIOLOGY,13(1),112-120.
MLA Liu, Zhaofei,et al."Specific Targeting of Human Integrin alpha(v)beta(3) with In-111-Labeled Abegrin (TM) in Nude Mouse Models".MOLECULAR IMAGING AND BIOLOGY 13.1(2011):112-120.
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