CASIA OpenIR  > 中国科学院分子影像重点实验室
Two Y-90-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy
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
Source PublicationMOLECULAR PHARMACEUTICS
2011-03-01
Volume8Issue:2Pages:591-599
SubtypeArticle
AbstractWe 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.
KeywordIntegrin Alpha(v)Beta(3) Arg-gly-asp (Rgd) Y-90 Tumor Radionuclide Therapy
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordPOSITRON-EMISSION-TOMOGRAPHY ; IMPROVING TUMOR UPTAKE ; SMALL-ANIMAL PET ; ALPHA(V)BETA(3) INTEGRIN ; CANCER-PATIENTS ; PEG(4) LINKERS ; ANGIOGENESIS ; EXPRESSION ; DIMERS ; PHARMACOKINETICS
Indexed BySCI
Language英语
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000289008600028
Citation statistics
Cited Times:25[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/9758
Collection中国科学院分子影像重点实验室
Corresponding AuthorWang, Fan
Affiliation1.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Dept Radiat Med, 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
GB/T 7714
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.
APA Liu, Zhaofei.,Shi, Jiyun.,Jia, Bing.,Yu, Zilin.,Liu, Yan.,...&Wang, Fan.(2011).Two Y-90-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy.MOLECULAR PHARMACEUTICS,8(2),591-599.
MLA Liu, Zhaofei,et al."Two Y-90-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy".MOLECULAR PHARMACEUTICS 8.2(2011):591-599.
Files in This Item: Download All
File Name/Size DocType Version Access License
90Y-RGD therapy (1).(4632KB)期刊论文作者接受稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Liu, Zhaofei]'s Articles
[Shi, Jiyun]'s Articles
[Jia, Bing]'s Articles
Baidu academic
Similar articles in Baidu academic
[Liu, Zhaofei]'s Articles
[Shi, Jiyun]'s Articles
[Jia, Bing]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Liu, Zhaofei]'s Articles
[Shi, Jiyun]'s Articles
[Jia, Bing]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 90Y-RGD therapy (1).pdf
Format: Adobe PDF
This file does not support browsing at this time
All comments (0)
No comment.
 

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