Department of Radiology, Taipei City Hospital, Taipei, Taiwan.
Mol Imaging Biol. 2010 Apr;12(2):145-54. doi: 10.1007/s11307-009-0248-6. Epub 2009 Jul 28.
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.
本研究旨在通过动态对比增强 MRI 验证叶酸受体（FR）靶向树枝状大分子，PEG-G3-(Gd-DTPA)11-(叶酸)5，检测 FR 阳性肿瘤的能力。
将荧光素标记的树枝状大分子与 KB 细胞、FR siRNA 敲低的 KB 细胞和 FR 阴性 HT-1080 细胞孵育，观察细胞摄取情况。对携带 KB 和 HT-1080 肿瘤的小鼠进行动态对比增强 MRI，分析增强模式和参数。
细胞摄取实验中，KB 细胞中可见绿色荧光，但在其他情况下未见。在动态对比增强 MRI 中，KB 肿瘤的 30 分钟洗脱百分比为-4±18%，HT-1080 肿瘤为 39±23%。17%的截断值可使灵敏度达到 94.4%，特异性达到 93.8%。
我们已经证明了 PEG-G3-(Gd-DTPA)11-(叶酸)5 在体外和体内的靶向能力。30 分钟洗脱百分比的 17%截断值可作为 FR 阳性肿瘤诊断的有用参数。
