摘要
目的：选择积聚于特定组织或器官的MRI靶向对比剂是提高MRI诊断准确性、敏感性的有效方法。尝试制备Gd-DTPA聚氰基丙烯酸正丁酯纳米微粒（Gd-PBCA-NP）肝脏靶向性对比剂，在动物实验中考察其肝脏靶向强化效果，并探讨其潜在的应用价值。
方法：实验于2004-09/2005-01在南方医院影像中心实验室完成。①采用阴离子乳化聚合法制备Gd-PBCA-NP。②用Malvern-3000HS激光粒度分析仪测定粒径及其分布。③采用高频电感耦合等离子发射光谱法（ICP-AES）测定透析液中Gd离子浓度，计算Gd-PBCA-NP的包封率及载药量。④透射电镜观察Gd-PBCA-NP的形态。⑤Gd-PBCA-NP肝脏靶向性实验：选择清洁级Wistar大鼠18只，采用随机数字法分为3组，Gd-DTPA对照组、PBCA-NP组、Gd-PBCA-NP组，每组6只。MRI扫描采用头部线圈，冠状及横断面扫描，平扫后，各组分别于注药后5，15，30 min，1，2 h增强扫描，扫描参数同平扫。计算肝脏各时间点强化率。
结果：①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。②Gd-PBCA-NP平均粒径65.7 nm，粒径分布为0.09。③Gd-PBCA-NP平均包封率和载药量分别为81.97%，51.23%。④Gd-DTPA对照组大鼠注射后5，15 min肝实质强化程度平均为35.2%，48.6%，同时可见肾实质也明显强化；注射30 min肝实质信号强度恢复到平扫前水平。Gd-PBCA-NP组注射后5 min，肝实质强化程度平均为3.4%；注射15，30 min，1，2 h肝实质强化程度平均为22.7%，36.1%，56.4%，24.8%。PBCA-NP组肝实质无强化。Gd-PBCA-NP组与Gd-DTPA组、PBCA-NP组肝实质强化方式明显不同。
结论：Gd-PBCA-NP是一种有效的肝实质特异性对比剂，能够靶向强化肝组织，提高了MRI诊断的准确性。
关键词：纳米微粒；磁共振；对比剂；聚氰基丙烯酸正丁酯；生物材料

吕国士，许乙凯.新型MR特异性对比剂Gd-聚氰基丙烯酸正丁酯纳米微粒的合成及其肝脏靶向性作用[J].中国组织工程研究与临床康复，2008，12(1):43-46 [www.zglckf.com/zglckf/ejournal/upfiles/08-1/1k-43(ps).pdf]

Gd-polybutylcyanoacrylate nanoparticle as a novel MR specific contrast agent: Synthesis and target for the liver

Abstract

AIM：It is selecting MRI targeted contrast agent accumulated on certain tissues or organs that contributes to increase the accuracy and sensitivity of MRI diagnosis. This study prepared polybutylcyanoacrylate nanoparticles (PBCA-NP) loaded with Gd-DTPA as targeted contrast agents, investigated the enhancement for the liver in animal experiment, and debated the potential value of its application.
METHODS: The experiment was finished in the Imaging Center of Nanfang Hospital between September 2004 and January 2005.①Gd-PBCA-NP were prepared by anionic emulsion polymerization.②The size and distribution of Gd-PBCA-NP were measured by Malvern-3000HS laser analyzer.③High-frequency inductively coupled plasma-atomic emission spectrometry was used to detect Gd ionic concentration in the dialysate, and then the encapsulation efficiency and loading capacity of Gd-PBCA-NP were calculated.④The morphology of Gd-PBCA-NP was examined by transmission electron microscopy.⑤Targeting for the liver by Gd-PBCA-NP: Eighteen clean Wistar rats were divided into 3 groups (n=6) at random: Gd-DTPA control group, PBCA-NP group, Gd-PBCA-NP group. All MRI scanning in the coronal, transverse and plain plates were performed with a head coil. Immediately after contrast medium injection, dynamic enhanced MR images were obtained at 5 minutes, 15 minutes, 30 minutes, 1 hour, and 2 hours using the same imaging parameters as for the plain scanning. Enhancement ratio of liver was calculated in three groups.
RESULTS: ①The morphology of Gd-PBCA-NP was spherical with well-distributed size, intact surface and core-shell structure but without adherence between particles observed by transmission electron microscopy.②The average size of Gd-PBCA-NP was 65.7 nm and the index of size distribution was 0.09.③The average encapsulation efficiency and loading capacity of Gd-PBCA-NP were respectively 81.97% and 51.23%.④After injection of Gd-DTPA, the percentage of enhanced liver parenchyma was 35.2% and 48.6% at 5 and 15 minutes, respectively, and the kidney was obviously enhanced simultaneously; at 30 minutes, the enhancement of liver recovered to normal. After injection of Gd-PBCA-NP, the percentage of enhanced liver parenchyma was 3.4%, 22.7%, 36.1%, 56.4% and 24.8%, respectively. There were significant differences in the enhancement among Gd-PBCA-NP group, Gd-DTPA group and PBCA-NP group.
CONCLUSION: Gd-PBCA-NP is an effective contrast agent targeted for liver, and can be used for the enhanced liver tissues and increase the accuracy of MRI diagnosis.

Lü GS, Xu YK.Gd-polybutylcyanoacrylate nanoparticle as a novel MR specific contrast agent: Synthesis and target for the liver.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(1):43-46(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-1/1k-43(ps).pdf]