Study of functionalized gadolinium chelates as magnetic resonance imaging contrast agents

磁共振成像（MRI）是临床诊断的重要手段。为了增强组织对比度，已经使用基于钆螯合物的造影剂，然而，它们不能总是区分病变和正常部分。本研究的目的是开发具有高组织或病变选择性的造影剂。由于在二乙烯三胺五乙酸（DTPA）或四氮杂环十二烷四乙酸（DOTA）骨架上选择性地引入官能团比较困难，本研究采用苯甲醛衍生物与多胺合成的希夫碱，合成了三种螯合物：水杨醛衍生物与二乙烯三胺缩合得到相应的Shiff碱，然后在碱性条件下用等分子量的溴乙酸酯处理，得到单乙酸酯。用硼氢化钠还原亚胺双键，水解三胺得到目标产物（1），以对位取代苯甲醛和二亚乙基三胺为原料，经Shiff碱还原，胺羧甲基化得到相应的三乙酸衍生物（2）。水杨醛衍生物与三（2-氨基乙基）胺缩合得到三臂螯合物（3）.螯合物（1-3）的钆配合物的合成和磁性测量正在进行中.

Magnetic resonance imaging (MRI) is an important modality in clinical diagnosis. To enhance tissue contrasts, contrast agents based on gadolinium chelates have been used, however, they cannot always distinguish between lesions and normal parts. A purpose of this study is to develop contrast agents having a high tissue or lesion selectivity. Since it is difficult to selectively introduce functional groups onto diethylenetriaminepentaacetic acid (DTPA) or tetraazacyclododecanetetraacetic acid (DOTA) skeleton, the shiff's bases synthesized from benzaldehyde derivatives and polyamines were used in this study.Syntheses of three types of chelates are as follows: Condensation of salicylaldehyde derivative and diethylenetriamine gave the corresponding Shiff's base, which was then treated with equimolecular amount of bromoacetate in a basic condition to yield the monoacetate. The imine double bonds were reduced by sodium borohydride and the resulting triamine was hydrolyzed to give the desired product (1).Similarly, starting from p-substituted benzaldehyde and diethylenetriamine, reduction of the Shiff's base and then carboxymethylation of the amine gave the corresponding triacetic acid derivative (2).Furthermore, condensation of salicylaldehyde derivative and tris(2-aminoethyl)amine gave the triarmed chelate (3).Syntheses of gadolinium complexes of the chelates (1-3) and measurements of the magnetic properties are now in progress.