组织间隙注射Gd-PBCA纳米微粒鉴别良恶性淋巴结的实验研究

Differentiation of Metastatic from Benign Lymph Nodes with Interstitial Injection of Gd-PBCA Nanoparticles

目的:制备Gd-DTPA聚氰基丙烯酸正丁酯纳米微粒(Gd-PBCA-NP),组织间隙注射Gd-PBCA-NP,评估其在良恶性淋巴结诊断和鉴别诊断中的价值。方法:采用阴离子乳化聚合法制备Gd-PBCA-NP,测定其粒径及分布、包封率及载药量,透射电镜观察其形态。选取健康成年新西兰白兔12只,采用随机数字法将其分为反应性增生淋巴结组及肿瘤转移淋巴结组2组。MRI平扫后2只反应性增生淋巴结于兔后脚掌注射后第1、3、6、12、24和48h点扫描,其余为给药后第24h扫描。测量淋巴结大小、平扫及增强后各组淋巴结信号强度并作统计学分析,观察增强后各组淋巴结MRI表现。结果:透射电镜观察Gd-PBCA-NP呈类圆形,大小均匀,表面平滑完整,粒子之间无粘连,具有明显的核-壳结构,其平均粒径65.7nm,粒径分布为0.09,平均包封率和载药量分别为81.97%、51.23%。反应性增生淋巴结和肿瘤转移性淋巴结均制作成功,平扫两组淋巴结在4个序列图像上的SNR、大小差异均无显著性意义。组织间隙注射Gd-PBCA-NP后,反应性增生淋巴结信号强度呈缓慢上升,于24h左右达到高峰,在T1WI、T1WI FS上表现为显著均匀强化,而肿瘤转移淋巴结表现为不均匀强化或无强化,两组SNR对比差异有显著性意义;在T2WI、T2*WI像上两组均未见强化,两组对比差异无显著性意义。结论:组织间隙注射Gd-PBCA-NP后,反应性淋巴结与肿瘤转移性淋巴结表现出不同的强化特征,在良恶性淋巴结鉴别中具有潜在的应用价值。

Objective： To prepare polybutyleyanoaerylate （PBCA） nanopartieles loaded with Gd-DTPA （Gd-PBCA- NP） and evaluate the effect in differentiation of metastatic from benign lymph nodes after interstitial injection of Gd-PBCA- NP. Methods：Gd-PBCA-NP were prepared by anionic emulsion polymerization. The size and encapsulation efficiency and loading capacity of Gd-PBCA-NP were measured. The morphology of Gd-PBCA-NP was examined by transmission electron microscopy. 12 New Zealand White Rabbits were divided into 2 groups at random： reactive hyperplasis group and tumorbearing group. All MR imaging was performed. Two animals were scanned at 1h, 3h, 6h, 12h,24h,48h but the others were scanned at 24h after injection of contrast agents. The signal intensity and size of all lymph nodes was measured on different sequences of images before and after contrast enhancement. The enhanced appearance of lymph nodes was observed in two groups. Results： The morphology of Gd-PBCA-NP was oval shaped with core-shell structure without adherence between particles observed by transmission electron microscopy. The average size of Gd-PBCA-NP was 65. 7nm and the index of size distribution was 0.09. The average encapsulation efficiency and loading capacity of Gd-PBCA-NP were respective 81.97 %, 51.23%. The reactive hyperplasia and metastatic lymph node models in all New Zealand White Rabbits were successfully developed. On unenhanced images,the SNR and the size of lymph nodes had no significant difference in four sequences of images in two groups. After interstitial injection of Gd-PBCA-NP, the SNR of the reactive hyperplasia lymph nodes increased slowly, and the maximal enhancement occurred at 24 hour. The reactive hyperplasia lymph nodes demonstrated obviously homogenous enhancement while metastatic lymph nodes showed heterogeneous or no enhancement, there were significant difference in the SNR of lymph nodes on enhanced T1WI and T1 WI with FS images, but no significant difference on T2 WI and T2 ＊ WI images between two groups. Conclusion： After interstitial injection of Gd-PBCA-NP, metastatic lymph nodes showed different enhancing characteristics from those of reactive hyperplasia nodes and it has the potential value in differentiating metastatic from benign lymph nodes.