钆喷替酸葡甲胺-白蛋白的合成及间隙注射后MR淋巴造影的实验研究

Experiment on MR lymphograpy after subcutaneous injection of HSA-Gd-DTPA and its synthesis

目的:制备Gd3+标记的二乙三胺五乙酸-白蛋白(钆喷替酸葡甲胺-白蛋白,Gd-DTPA-HSA),在动物实验中观察其淋巴结靶向强化效果,并探讨其潜在的应用价值。方法:①选定4个不同pH值的反应体系及不同的cDTPAa/HSA摩尔比率,测定不同反应条件下每个白蛋白分子上所结合的Gd3+离子数量,计算不同反应条件DTPA-HSA的偶联效率;②健康新西兰兔6只,平扫后在双侧后脚掌趾蹼间隙各注射0.2ml Gd-DTPA-HSA,给药后第30min、1h、3h扫描。相关参数与平扫时相同。测量增强前后窝淋巴结的信号强度并计算其强化率。结果:①在cDTPAa/HSA摩尔比相同的条件下,每分子HSA-DTPA结合的Gd3+数目和DTPA-HSA的偶联效率随着反应体系pH值的增高而增加;②在反应体系pH值一定的条件下,cDTPAa/HSA摩尔比为200:1的条件下每分子HSA-DTPA结合的Gd3+数量大于二者摩尔比为100:1时所结合的Gd3+数量,但前者的DTPA-HSA偶联效率低于后者;③经趾蹼间隙给药后,小腿淋巴管和窝淋巴结明显、均匀的强化。结论:pH=8.0的0.1M NaHCO3反应缓冲体系有利于HSA与DTPA的偶联反应。HSA-Gd-DTPA是一种有效的淋巴结特异性对比剂,能够靶向强化淋巴结。

Objective：To prepare gadoliniumion labeled Diethylenetriaminepentaacetic acid（DTPA）-coupled human serum albumin（HSA）,to investigate the enhancement effect on the lymph node in animal experiment,and to explore the potential value of its application.Methods：① The number and coupling efficacy of HSAcoupled of gadolinium ions were analyzed at different cDTPAa-to-HSA molar ratios and in buffer solutions of different pH values;② Six New Zealand rabbits underwent the MRI examination before and after subcutaneous injection of HSA-Gd-DTPA to study the MR lymphography of the popliteal lymph nodes.The post-contrast scanning started at 10 min,30 min and 60 min after injection of HSA-Gd-DTPA,with identical imaging parameters.The signal intensity of popliteal lymph node was measured and the enhancement rate was calculated.Results：① The number and coupling efficacy of HSA-coupled of gadolinium ions increased with the pH value of the reaction system at the same cDTPAa-to-HSA molar ratio;② At the same pH value of the reaction system,the number of HSA-coupled of gadolinium ions increased with the cDTPAa-to-HSA molar ratios,whereas,the coupling efficancy of HSA-coupled of gadolinium ions decreased;③ After subcutaneous injection,HSA-Gd-DTPA entered the lymph vessel,causing obvious homogeneous enhancement of the lymphatic vessels and popliteal lymph nodes.Conclusion：The number and coupling efficacy of HSA-coupled of gadolinium ions depend on the pH value of the reaction system and cDTPAa-to-HSA molar ratio.HSA-Gd-DTPA is an effective contrast agent targeted for lymph node after subcutaneous administration.