Two (90)Y-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy

	Two (90)Y-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy
	Liu, ZF; Shi, JY; Jia, B; Yu, ZL; Liu, Y; Zhao, HY; Li, F; Tian, J; Chen, XY; Liu, SA; Wang, F; Wang, Fan
发表期刊	MOLECULAR PHARMACEUTICS
	2011
卷号	8 期号:2 页码:591-599
摘要	We have recently developed a series of new Arg-Gly-Asp (RGD) dimeric peptides for specific targetingof integrin Rvβ3 with enhanced tumor uptake and improved pharmacokinetics. In this study, we investigated 90Y-labeled RGD tetramer (RGD4) and the new type of RGD dimer (3PRGD2), for the radionuclide therapy of integrin Rvβ3-positive tumors. Biodistribution and gamma imaging studies of 111In labeled RGD4 and 3PRGD2 were performed. Groups of nude mice were used to determine maximum tolerated dose (MTD) of 90Y-DOTA-RGD4 and 90Y-DOTA-3PRGD2. The radionuclide therapeutic efficacy of 90Y-DOTA-RGD4 and 90Y-DOTA-3PRGD2 was evaluated in U87MG tumor-bearing nude mice. The U87MG tumor uptake of 111In-DOTA-3PRGD2 was slightly lower than that of the 111In-DOTA-RGD4 (e.g., 6.13 ( 0.82%ID/g vs 6.43 ( 1.6%ID/g at 4 h postinjection),but the uptake of 111In-DOTA-3PRGD2 in normal organs, such as liver and kidneys, was much lower than that of 111In-DOTA-RGD4, which resulted in much higher tumor-to-nontumor ratios and lower toxicity. The MTD of 90Y-DOTARGD4 in nude mice is less than 44.4 MBq, while the MTD of 90Y-DOTA-3PRGD2 in mice is more than 55.5 MBq. 90Y-DOTA- 3PRGD2 administration exhibited a similar tumor inhibition effect as compared with 90Y-DOTA-RGD4 at the same dose. The tumor vasculature in the 90Y-DOTA-3PRGD2 treatment group was much less than the control groups. Radionuclide therapy studies exhibited that both 90Y-DOTA-RGD4 and 90Y-DOTA-3PRGD2 caused significant tumor growth delay in the U87MG tumor model. Compared to 90Y-DOTA-RGD4, the low accumulation of 90Y-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.
关键词	Radionuclide Therapy 90y Integrin Rvβ3 Arg-gly-asp (Rgd)
收录类别	SCI
WOS记录号	WOS:289008600028
引用统计
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/3990
专题	中国科学院分子影像重点实验室
通讯作者	Wang, Fan
推荐引用方式 GB/T 7714	Liu, ZF,Shi, JY,Jia, B,et al. Two (90)Y-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy[J]. MOLECULAR PHARMACEUTICS,2011,8(2):591-599.
APA	Liu, ZF.,Shi, JY.,Jia, B.,Yu, ZL.,Liu, Y.,...&Wang, Fan.(2011).Two (90)Y-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy.MOLECULAR PHARMACEUTICS,8(2),591-599.
MLA	Liu, ZF,et al."Two (90)Y-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy".MOLECULAR PHARMACEUTICS 8.2(2011):591-599.

条目包含的文件		下载所有文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
90Y-RGD therapy.pdf（4632KB）	期刊论文	作者接受稿	开放获取	CC BY-NC-SA	浏览下载