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Anti-tumor Effect of Integrin Targeted Lu-177-3PRGD(2) and Combined Therapy with Endostar
Shi, Jiyun1,2; Fan, Di1,3; Dong, Chengyan1,3; Liu, Hao1,3; Jia, Bing1,3; Zhao, Huiyun1,2; Jin, Xiaona4; Liu, Zhaofei1,3; Li, Fang4; Wang, Fan1,3
关键词Integrin alpha(v)beta(3) Arg-Gly-Asp (RGD) Lu-177 radionuclide therapy combination therapy
刊名THERANOSTICS
2014
DOI10.7150/thno.7781
4期:3页:256-266
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]IMPROVING TUMOR UPTAKE ; RGD PEPTIDES ; NEUROENDOCRINE TUMORS ; CANCER ; RADIOTHERAPY ; EXPRESSION ; EFFICACY ; MODEL ; RADIOIMMUNOTHERAPY ; CHEMORADIOTHERAPY
英文摘要

Purpose: Targeted radiotherapy (TRT) is an emerging approach for tumor treatment. Previously, 3PRGD(2) (a dimeric RGD peptide with 3 PEG(4) linkers) has been demonstrated to be of advantage for integrin alpha(v)beta(3) targeting. Given the promising results of Tc-99m-3PRGD(2) for lung cancer detection in human beings, we are encouraged to investigate the radiotherapeutic efficacy of radiolabeled 3PRGD(2). The goal of this study was to investigate and optimize the integrin alpha(v)beta(3) mediated therapeutic effect of Lu-177-3PRGD(2) in the animal model.

Experimental Design: Biodistribution, gamma imaging and maximum tolerated dose (MTD) studies of Lu-177-3PRGD(2) were performed. The targeted radiotherapy (TRT) with single dose and repeated doses as well as the combined therapy of TRT and the anti-angiogenic therapy (AAT) with Endostar were conducted in U87MG tumor model. The hematoxylin and eosin (H&E) staining and immunochemistry (IHC) were performed post-treatment to evaluate the therapeutic effect.

Results: The U87MG tumor uptake of Lu-177-3PRGD(2) was relatively high (6.03 +/- 0.65 % ID/g, 4.62 +/- 1.44 % ID/g, 3.55 +/- 1.08 % ID/g, and 1.22 +/- 0.18 % ID/g at 1 h, 4 h, 24 h, and 72 h postinjection, respectively), and the gamma imaging could visualize the tumors clearly. The MTD of Lu-177-3PRGD(2) in nude mice (> 111 MBq) was twice to that of Y-90-3PRGD(2) (55.5 MBq). U87MG tumor growth was significantly delayed by Lu-177-3PRGD(2) TRT. Significantly increased anti-tumor effects were observed in the two doses or combined treatment groups.

Conclusion: The two-dose TRT and combined therapy with Endostar potently enhanced the tumor growth inhibition, but the former does not need to inject daily for weeks, avoiding a lot of unnecessary inconvenience and suffering for patients, which could potentially be rapidly translated into clinical practice in the future.

语种英语
WOS记录号WOS:000334663900003
项目编号81125011 ; 2013CB733802 ; 2011CB707703 ; 81000625 ; 30930030 ; 81222019 ; 30900373 ; 81201127 ; 81028009 ; 81321003 ; 2012ZX09102301-018 ; 2011YQ030114 ; 2012BAK25B03-16 ; 31300 ; BMU20110263
资助机构Outstanding Youth Fund ; "973" program ; National Natural Science Foundation of China (NSFC) ; Ministry of Science and Technology of China ; Ministry of Education of China
引用统计
被引频次:11[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/400002259/60113
专题北京大学医药卫生分析中心
北京大学基础医学院
北京大学口腔医学院_中心实验室
作者单位1.Peking Univ, Dept Radiat Med, Beijing 100191, Peoples R China
2.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Med & Healthy Analyt Ctr, Beijing 100191, Peoples R China
4.Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing 100857, Peoples R China
推荐引用方式
GB/T 7714
Shi, Jiyun,Fan, Di,Dong, Chengyan,et al. Anti-tumor Effect of Integrin Targeted Lu-177-3PRGD(2) and Combined Therapy with Endostar[J]. THERANOSTICS,2014,4(3):256-266.
APA Shi, Jiyun.,Fan, Di.,Dong, Chengyan.,Liu, Hao.,Jia, Bing.,...&Wang, Fan.(2014).Anti-tumor Effect of Integrin Targeted Lu-177-3PRGD(2) and Combined Therapy with Endostar.THERANOSTICS,4(3),256-266.
MLA Shi, Jiyun,et al."Anti-tumor Effect of Integrin Targeted Lu-177-3PRGD(2) and Combined Therapy with Endostar".THERANOSTICS 4.3(2014):256-266.
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