Dynamic Contrast-Enhanced Folate-Receptor-Targeted MR Imaging Using a Gd-loaded PEG-Dendrimer-Folate Conjugate in a Mouse Xenograft Tumor Model

被引:26
作者
Chen, Wei-Tsung [1 ,2 ]
Thirumalai, Dhakshanamurthy [3 ]
Shih, Tiffany Ting-Fang [1 ,4 ]
Chen, Ran-Chou [2 ,5 ]
Tu, Shin-Yang [2 ]
Lin, Chin-I [3 ]
Yang, Pang-Chyr [6 ,7 ]
机构
[1] Natl Taiwan Univ, Sch Med, Dept Radiol, Taipei 10764, Taiwan
[2] Taipei City Hosp, Dept Radiol, Taipei, Taiwan
[3] Ind Technol Res Inst, Union Chem Lab, Hsinchu, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei, Taiwan
[5] Natl Yang Ming Univ, Dept Biomed Imaging & Radiol Sci, Taipei 112, Taiwan
[6] Natl Taiwan Univ Hosp, Dept Med, Taipei, Taiwan
[7] Natl Taiwan Univ, Sch Med, Dept Med, Taipei 10764, Taiwan
关键词
Molecular imaging; Dendrimer; Folate receptor; MRI; MEDIATED ENDOCYTOSIS; KB-CELLS; NANOPARTICLES; EXPRESSION; CANCER; AGENTS; DIFFERENTIATION; DELIVERY; ALPHA; OVARY;
D O I
10.1007/s11307-009-0248-6
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
The purpose of this study is to validate a folate-receptor (FR)-targeted dendrimer, PEG-G3-(Gd-DTPA)11-(folate)5, for its ability to detect FR-positive tumors, by using dynamic contrast-enhanced MRI. KB cells, FR siRNA knockdown KB cells, and FR negative HT-1080 cells, were incubated with fluorescein-labeled dendrimer and their cellular uptake was observed. Dynamic contrast-enhanced MRI was performed on mice-bearing KB and HT-1080 tumors and the enhancement patterns and parameters were analyzed. Green fluorescence was found in the KB cells in the cellular uptake experiment, but was not seen in other settings. In the dynamic contrast-enhanced MRI, the 30-min washout percentage was -4 +/- 18% in the KB tumors and 39 +/- 23% in the HT-1080 tumors. A 17% cut-off point gave a sensitivity of 94.4% and a specificity of 93.8%. We have demonstrated the targeting ability of PEG-G3-(Gd-DTPA)11-(folate)5 in vitro and in vivo. A 17% cut-off point for a 30-min washout percentage can be a useful parameter for the diagnosis of FR-positive tumors.
引用
收藏
页码:145 / 154
页数:10
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