北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学医药卫生分析中心  > 期刊论文
学科主题: 公共卫生
题名:
Improving Tumor-Targeting Capability and Pharmacokinetics of Tc-99m-Labeled Cyclic RGD Dimers with PEG(4) Linkers
作者: Wang, Lijun1; Shi, Jiyun1; Kim, Young-Seung1; Zhai, Shizhen1; Jia, Bing2; Zhao, Huiyun2; Liu, Zhaofei3; Wang, Fan2; Chen, Xiaoyuan3; Liu, Shuang1
关键词: Integrin alpha(v)beta(3) ; Tc-99m-labeled peptides ; cyclic RGD dimers ; tumor imaging
刊名: MOLECULAR PHARMACEUTICS
发表日期: 2009
DOI: 10.1021/mp800150r
卷: 6, 期:1, 页:231-245
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]: GLIOMA INTEGRIN-ALPHA(V)BETA(3) EXPRESSION ; INTEGRIN ALPHA(V)BETA(3) EXPRESSION ; CANCER ALPHA(V)-INTEGRIN EXPRESSION ; RECEPTOR ANTAGONIST USEFUL ; TERNARY LIGAND SYSTEM ; BREAST-CANCER ; BIODISTRIBUTION CHARACTERISTICS ; BIOLOGICAL EVALUATION ; INITIAL EVALUATION ; F-18-LABELED RGD
英文摘要:

This report describes the synthesis of two cyclic RGD (Arg-Gly-Asp) conjugates, HYNIC-2PEG(4)-dimer (HYNIC = 6-hydrazinonicotinyl; 2PEG(4)-dimer = E[PEG(4)-c(RGDfK)](2); and PEG(4) = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and HYNIC-3PEG(4)-dimer (3PEG(4)-dimer = PEG(4)-E[PEG(4)-c(RGDfK)](2)), and evaluation of their Tc-99m complexes [Tc-99m(HYNIC-2PEG(4)-dimer)(tricine)(TPPTS)] (Tc-99m-2PEG(4)-dimer: TPPTS = trisodium triphenylphosphine-3,3′,3 ′′-trisulfonate) and [Tc-99m(HYNIC-3PEG(4)-dimer)(tricine)(TPPTS)] (Tc-99m-3PEG(4)-dimer) as novel radiotracers for imaging integrin alpha(v)beta(3) expression in athymic rude mice bearing U87MG glioma and MDA-MB-435 breast cancer xenografts. The integrin alpha(v)beta(3) binding affinities of RGD peptides were determined by competitive displacement of I-125-c(RGDyK) on U87MG glioma cells. It was found that the two PEG4 linkers between RGD motifs in HYNIC-2PEG(4)-dimer (IC50 = 2.8 +/- 0.5 nM) and HYNIC-3PEG(4)-dimer (IC50 = 2.4 +/- 0.7 nM) are responsible for their higher integrin alpha(v)beta(3) binding affinity than that of HYNIC-PEG(4)-dimer (PEG(4)-dimer = PEG(4)-E[c(RGDfK)](2); IC50 = 7.5 +/- 2.3 nM). Addition of extra PEG(4) linker in HYNIC-3PEG(4)-dimer has. little impact on integrin alpha(v)beta(3) binding affinity. Tc-99m-2PEG(4)-dimer and Tc-99m-3PEG(4)-dimer were prepared in high yield with >95% radiochemical purity and the specific activity of > 10 CI/mu mol. Biodistribution :studies clearly demonstrated that PEG(4) linkers are particularly useful for improving the tumor uptake and clearance kinetics of 99mTc-2PEG4-dimer and Tc-99m-3PEG(4)-dimer from noncancerous organs. It was also found that there was a linear relationship between the tumor size and radiotracer tumor uptake expressed as %ID (percentage of the injected dose) in U87MG glioma and MDA-MB-435 breast tumor models. The blocking experiment showed that the tumor uptake of Tc-99m-2PEG(4)-dimer is integrin alpha(v)beta(3)-mediated. In the metabolism study, Tc-99m-2PEG(4)-dimer had high metabolic stability during its excretion from renal and hepatobiliary routes. Tc-99m-3PEG(4)-dimer also remained intact during thee excretion from the renal route, but, had similar to 30% metabolism during the excretion from the hepatobiliary route. Planar imaging studies in U87MG glioma and MDA-MB-435 breast tumor models showed that the tumors of similar to 5 mm in diameter could be readily visualized with excellent contrast. Thus, Tc-99m-3PEG(4)-dimer is a very promising radiotracer for the early detection of integrin alpha(v)beta(3)-positive tumors, and may have the potential for noninvasive monitoring of tumor growth or treatment efficacy.

语种: 英语
所属项目编号: R01 CA115883 A2 ; R21 EB003419-02 ; R21 HL083961-01 ; DE-FG02-08ER64684 ; R01 CA119053
项目资助者: Purdue University ; National Cancer Institute ; National Institute of Biomedical Imaging and Bioengineering ; National Heart, Lung, and Blood Institute ; Department of Energy ; NCI
WOS记录号: WOS:000263035000024
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60875
Appears in Collections:北京大学医药卫生分析中心_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA
2.Peking Univ, Med Isotopes Res Ctr, Beijing 100083, Peoples R China
3.Stanford Univ, Mol Imaging Program Stanford, Dept Radiol & BioX, Stanford, CA USA

Recommended Citation:
Wang, Lijun,Shi, Jiyun,Kim, Young-Seung,et al. Improving Tumor-Targeting Capability and Pharmacokinetics of Tc-99m-Labeled Cyclic RGD Dimers with PEG(4) Linkers[J]. MOLECULAR PHARMACEUTICS,2009,6(1):231-245.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wang, Lijun]'s Articles
[Shi, Jiyun]'s Articles
[Kim, Young-Seung]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wang, Lijun]‘s Articles
[Shi, Jiyun]‘s Articles
[Kim, Young-Seung]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace