Liu Yongjun, Wu Xiaoyun, Sun Xiaohe, Wang Dan, Zhong Ying, Jiang Dandan, Wang Tianqi, Yu Dexin, Zhang Na
School of Pharmaceutical Science, Shandong University.
Department of Radiology Medicine, Qilu Hospital, Jinan, People's Republic of China.
Int J Nanomedicine. 2017 Jul 14;12:5039-5052. doi: 10.2147/IJN.S131878. eCollection 2017.
Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, <0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM s) was observed compared to Magnevist (4.9 mM s; <0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor.
开发具有高弛豫率和特异性的磁共振成像（MRI）造影剂对于提高MRI诊断的敏感性和准确性至关重要。在本研究中，设计并制备了一种MRI造影剂，即血管内皮生长因子受体（VEGFR）靶向的聚（L-赖氨酸）（PLL）-二乙烯三胺五乙酸（DTPA）-钆（Gd）（VEGFR靶向的PLL-DTPA-Gd，VPDG），以增强肿瘤的MRI诊断能力。首先合成生物素-PLL-DTPA-Gd，然后利用生物素-抗生物素蛋白反应将VEGFR抗体连接到生物素-PLL-DTPA-Gd上。体外细胞毒性研究结果表明，在实验浓度下，VPDG对MCF-7细胞和HepG2细胞的毒性较低。在细胞摄取实验中，与PLL-DTPA-Gd（PDG）相比，VPDG可显著提高VEGFR阳性HepG2细胞的内化率（61.75%±5.22%）（25.16%±4.71%，<0.05）。在体外MRI研究中，观察到其T1弛豫率（14.184 mM s）明显高于马根维显（4.9 mM s；<0.01）。此外，体内MRI研究结果表明，VPDG可显著增强肿瘤信号强度并延长诊断时间（从<1小时延长至2.5小时）。这些结果表明，大分子VPDG是一种有前景的MRI造影剂，在肿瘤分子诊断方面具有巨大潜力。
