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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
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
Indexed BySCI
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000289008600028
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Cited Times:25[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
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.
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