血管内皮生长因子MR靶向对比剂的制备及其在乳腺癌裸鼠模型的MR实验研究

Preparation of MR Contrast Agent of Vascular Endothelial Growth Factor Rectptor-targeted and its Experimental Study in MR Imaging in the Mice Model Implanted with Breast Cancer

目的制备靶向血管内皮生长因子(VEGF)受体的Gd-DTPA脂质体及其对裸鼠乳腺癌移植瘤的靶向性实验研究。方法制备出VEGF抗体标记的Gd-DTPA脂质体,检测其理化性质。将16只乳腺癌移植瘤的裸鼠分为2组(n=8),分别经鼠尾静脉注射Gd-DTPA、抗VEGF-Gd-DTPA脂质体后0.5h、2h、4h、6h、12h、24h行磁共振成像扫描,计算肿瘤强化值。结果所制备的抗VEGF-Gd-DTPA脂质体具有纳米颗粒的特征,在动物实验研究上GdDTPA组强化峰值出现在0.5h,相对强化值为1.34±0.46;抗VEGF-Gd-DTPA脂质体组强化峰值均出现在2h,相对强化值为2.15±0.52。2组乳腺癌移植瘤2h、4h、8h、24h扫描时间点相对强化值比较,差异有统计学意义(P<0.05),抗VEGF-GdDTPA组增强值高。结论 VEGF抗体修饰的Gd-DTPA脂质体能与肿瘤体内血管内皮因子受体结合,为肿瘤血管生成的影像诊断提供了新的思路。

Objective To prepare target Vascular Endothelial Growth Factor-Rectptor gadopentetate dimeglumine liposome and study in MR imaging in the Mice Model implanted with breast Cancer. Methods Anti-VEGF-Gd-DTPA liposome was prepared, and the physical and chemical properties were detected.The Breast cancer transplantated nude mice were divided into 2 groups（n=8）. Anti-VEGF-Gd-DTPA liposome and Gd-DTPA were injected into the nude mice. After 30 min, 2h, 4h, 8h, 24 h, The tumor enhancement rate was calculated. Results The prepared Anti-VEGF-Gd-DTPA liposomes were characterized as nanoparticles. In vivo MRI, The group of Gd-DTPA resulted in a maximum tumor REV of 1.34±0.46 at 30 min, The group of anti-VEGFGd-DTPA liposome resulted in a maximum tumor REV of 2.15±0.52 at 2h. In 2 groups of breast cancer, 2, 4, 8h,24 h scan time points were compared, the difference was statistically significant（P〈0.05）, the anti-VEGF-Gd-DTPA group was the highest REV. Conclusion VEGF antibody modified Gd-DTPA liposome can target the tumor vascular endothelial growth factor-receptor, which provides a new way of the tumor angiogenesis imaging diagnosis.