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学科主题: 公共卫生
题名:
Two Y-90-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy
作者: Liu, Zhaofei1,2; Shi, Jiyun1,2; Jia, Bing1,2; Yu, Zilin1,2; Liu, Yan1,2; Zhao, Huiyun1,2; Li, Fang3; Tian, Jie4; Chen, Xiaoyuan5; Liu, Shuang6; Wang, Fan1,2
关键词: integrin alpha(v)beta(3) ; Arg-Gly-Asp (RGD) ; Y-90 ; tumor ; radionuclide therapy
刊名: MOLECULAR PHARMACEUTICS
发表日期: 2011-03-01
DOI: 10.1021/mp100403y
卷: 8, 期:2, 页:591-599
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: POSITRON-EMISSION-TOMOGRAPHY ; IMPROVING TUMOR UPTAKE ; SMALL-ANIMAL PET ; ALPHA(V)BETA(3) INTEGRIN ; CANCER-PATIENTS ; PEG(4) LINKERS ; ANGIOGENESIS ; EXPRESSION ; DIMERS ; PHARMACOKINETICS
英文摘要:

We have recently developed a series of new Arg-Gly-Asp (RGD) dimeric peptides for specific targeting of integrin alpha(v)beta(3) with enhanced tumor uptake and improved pharmacokinetics. In this study, we investigated Y-90-labeled RGD tetramer (RGD4) and the new type of RGD dimer (3PRGD2), for the radionuclide therapy of integrin alpha(v)beta(3)-positive tumors. Biodistribution and gamma imaging studies of In-111 labeled RGD4 and 3PRGD2 were performed. Groups of nude mice were used to determine maximum tolerated dose (MTD) of Y-90-DOTA-RGD4 and Y-90-DOTA-3PRGD2. The radionuclide therapeutic efficacy of Y-90-DOTA-RGD4 and 90Y-DOTA-3PRGD2 was evaluated in U87MG tumor-bearing nude mice. The U87MG tumor uptake of In-111-DOTA-3PRGD2 was slightly lower than that of the In-111-DOTA-RGD4 (e.g., 6.13 +/- 0.82%ID/g vs 6.43 +/- 1.6%ID/g at 4 h post-injection), but the uptake of In-111-DOTA-3PRGD2 in normal organs, such as liver and kidneys, was much lower than that of In-111-DOTA-RGD4, which resulted in much higher tumor-to-nontumor ratios and lower toxicity. The MTD of Y-90-DOTA-RGD4 in nude mice is less than 44.4 MBq, while the MTD of Y-90-DOTA-3PRGD2 in mice is more than 55.5 MBq. Y-90-DOTA-3PRGD2 administration exhibited a similar tumor inhibition effect as compared with Y-90-DOTA-RGD4 at the same dose. The tumor vasculature in the Y-90-DOTA-3PRGD2 treatment group was much less than the control groups. Radionuclide therapy studies exhibited that both Y-90-DOTA-RGD4 and Y-90-DOTA-3PRGD2 caused significant tumor growth delay in the U87MG tumor model. Compared to Y-90-DOTA-RGD4, the low accumulation of Y-90-DOTA-3PRGD2 in normal organs led to lower toxicity and higher MTD in nude mice, which would make it more suitable for high dose or multiple-dose regimens, in order to achieve maximum therapeutic efficacy.

语种: 英语
所属项目编号: 30870728 ; 30930030 ; 30900373 ; 81000625 ; 81028009 ; 2007AA02Z467 ; 2011CB70-7703 ; 2009ZX09103-733 ; 2009ZX09301-010 ; 2009ZX-09103-746
项目资助者: NSFC ; "863" project ; "973" project ; Ministry of Science and Technology of China
WOS记录号: WOS:000289008600028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64739
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.Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing 100857, Peoples R China
4.Chinese Acad Sci, Med Image Proc Grp, Inst Automat, Beijing 100190, Peoples R China
5.Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA
6.Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA

Recommended Citation:
Liu, Zhaofei,Shi, Jiyun,Jia, Bing,et al. Two Y-90-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy[J]. MOLECULAR PHARMACEUTICS,2011,8(2):591-599.
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