一种大环类双核非离子型磁共振对比剂的合成及弛豫性能  

Synthesis and Relaxivity of One Macrocyclic Binuclear Nonionic Magnetic Resonance Contrast Agent

作　　者：周进 孙宏顺 李玉龙 蒋蕻 郭成 沈临江 Zhou Jin;Sun Hongshun;Li Yulong;Jiang Hong;Guo Cheng;Shen Linjiang(College of Chemistry and Molecular Engineering,Nanjing Tech University,Nanjing 211816;Targeted MRI Contrast Agents Laboratory of Jiangsu Province,Nanjing Polytechnic Institute,Nanjing 210048;School of Physical and Mathematical Sciences,Nanjing Tech University,Nanjing 211816)

机构地区：[1]南京工业大学化学与分子工程学院,南京211816 [2]南京科技职业学院江苏省磁共振靶向显像剂工程实验室,南京210048 [3]南京工业大学数理科学学院,南京211816

出　　处：《有机化学》2021年第7期2767-2773,共7页Chinese Journal of Organic Chemistry

基　　金：江苏省自然科学基金(No.BK20181486);江苏省高校自然科学基金(No.17KJB320001);江苏省高校优秀中青年教师和校长境外研修计划和江苏省青蓝工程资助项目.

摘　　要：磁共振成像技术被广泛应用于诊断医学和软组织成像,而磁共振对比剂有助于提高成像对比度.报道了一种基于钆-DOTA-酰肼结构(DOTA=1,4,7,10-四氮杂环十二烷^(-1),4,7,10-四乙酸)的新型双核非离子型磁共振对比剂(Gd-DOTAH)2-SBDC的设计、合成及弛豫性能.在0.5 T磁场下,测得其纵向弛豫率为每分子10.6 L•mmol^(-1)•s^(-1)或5.3 L•mmol^(-1)•Gd^(-1)•s^(-1),高于目前临床使用的单核大环对比剂钆-DOTA.体外磁共振成像研究显示该磁共振对比剂具有提高诊断灵敏度和准确度的特点.同时,该对比剂分子中含有能与髓鞘特异性结合的二苯乙烯结构,具有成为髓鞘靶向磁共振对比剂的应用潜力.另外,探讨了该对比剂的两条合成路线(A和B),总收率分别为70%和75%.综合考虑适用性,合成路线B更优.Magnetic resonance imaging(MRI)is widely employed in diagnostic medicine and soft tissue imaging.Contrast agents(CAs)can improve the specificity of enhanced MRI images.Herein,the design,synthesis and relaxivity of a novel binuclear nonionic Gd-based DOTA-hydrazide(DOTA=1,4,7,10-tetraazacyclododecan^(-1),4,7,10-tetraacetic acid)derived MRI contrast agents,(Gd-DOTAH)2-SBDC,were reported.The improved longitudinal relaxivity was determined as 10.6 L•mmol^(-1)•s^(-1) per molecule or 5.3 L•mmol^(-1)•Gd^(-1)•s^(-1) at 0.5 T,which is higher than that of the mononuclear clinical macrocyclic agent Gd-DOTA.In vitro MRI studies confirmed its suitability for use as a MRI contrast agent with improved diagnostic sensitivity and accuracy.Furthermore,the stilbene moiety endows it with myelin-targeting capabilities.In addition,two synthetic routes(A and B)for this contrast agent were compared,providing overall yields of 70%and 75%,respectivily,and route B was deemed superior.

关 键 词：磁共振成像 对比剂 合成 弛豫率 DOTA-酰肼 钆-DOTA 髓鞘 

分 类 号：O657.2[理学—分析化学] R914[理学—化学]