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学科主题: 公共卫生
题名:
Anti-tumor Effect of Integrin Targeted Lu-177-3PRGD(2) and Combined Therapy with Endostar
作者: 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
发表日期: 2014
DOI: 10.7150/thno.7781
卷: 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
所属项目编号: 81125011 ; 2013CB733802 ; 2011CB707703 ; 81000625 ; 30930030 ; 81222019 ; 30900373 ; 81201127 ; 81028009 ; 81321003 ; 2012ZX09102301-018 ; 2011YQ030114 ; 2012BAK25B03-16 ; 31300 ; BMU20110263
项目资助者: Outstanding Youth Fund ; "973" program ; National Natural Science Foundation of China (NSFC) ; Ministry of Science and Technology of China ; Ministry of Education of China
WOS记录号: WOS:000334663900003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60113
Appears in Collections:北京大学医药卫生分析中心_期刊论文

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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

Recommended Citation:
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.
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