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新型MR网状内皮靶向对比剂Gd-PBCA纳米微粒的合成及与SPIO在MR淋巴成像的对比研究

Gd-PBCA Nanoparticles as Novel MR Contrast Agents Targeted Reticuloendothelial System: Synthesis and Comparison with SPIO in MR Lymphography

【作者】 吕国士

【导师】 许乙凯;

【作者基本信息】 第一军医大学 , 医学影像学, 2006, 博士

【摘要】 研究目的 一、制备Gd-DTPA聚氰基丙烯酸正丁酯纳米微粒(Gd-PBCA-NP),并优选出最佳的制备方案; 二、在动物实验中静脉注射Gd-PBCA-NP,并与Gd-DTPA对照,考察Gd-PBCA-NP肝脏靶向强化效果,并探讨其潜在的应用价值; 三、组织间隙注射Gd-PBCA-NP,进一步评估其淋巴组织靶向增强效果,并与SPIO网状内皮阴性对比剂对比,评估两者在MR淋巴成像中对良、恶性淋巴结诊断和鉴别诊断的价值。 材料和方法 一、Gd-PBCA-NP的制备及优化 (一)制备工艺的确定 采用阴离子乳化聚合法,精密称取一定量Gd-DTPA(V/V)、Dextron-70(W/V),溶于双蒸水中,用0.1N HCL调节PH于酸性状态,在磁力搅拌器下缓慢加入一定量PBCA单体(V/V),搅拌4h,然后加入一定量1N NaoH调节PH于7.0,反应终止,随后用0.45um微孔滤膜过滤,将滤液存于4℃冰箱内备用。 (二)单因素初选制备条件 在一定范围内,介质的PH值、单体浓度、稳定剂及药物浓度是影响NP粒径大小及其均匀度主要因素。固定其它三种因素于某一条件下,分别考察另一因素在不同条件下对Gd-PBCA-NP粒径及其均匀度的影响。

【Abstract】 Objective一、To prepare polybutylcyanoacrylate (PBCA) nanoparticles loaded with Gd-DTPA and optimize the preparative conditions.二、 Compared to Gd-DTPA, to investigate the effect of Gd-PBCA-NP as MR specific contrast agents targeted imaging for liver in animal experiment and debate the potential value of its clicinal application.三、To further evaluate the effect of Gd-PBCA-NP targeted lymphatic tissue and thevalue of the MR lymphography to differentiate metastatic from benign lymph nodeswas compared between Gd-PBCA-NP and SPIO as specific contrast agents forreticuloendothelial system after interstitial administration of Gd-PBCA-NP and SPIO.Materials and Methods一、Preparation and optimization of Gd-PBCA-NP(一) Determination the preparation technicsGd-PBCA-NP were prepared by anionic emulsion polymerization of monomeric PBCA (V/V) in an aqueous medium containing 0. 1N HCl and fixed quantity of

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