权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study of functionalized gadolinium chelates as magnetic resonance imaging contrast agents

功能化钆螯合物作为磁共振成像造影剂的研究

基本信息

批准号：
13640586
负责人：
USUI Shuji
金额：
$ 2.3万
依托单位：
Hiroshima International University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

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.

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，已经使用了基于Gd螯合物的造影剂，然而，它们并不总是区分病变和正常部位。本研究的目的是开发具有高组织或病变选择性的造影剂。由于在二乙烯三氨基五乙酸(DTPA)或四氮杂环十二烷四乙酸(DOTA)骨架上很难选择性地引入官能团，本研究采用苯甲醛衍生物和多胺合成的Shiff碱，合成了三种类型的络合物：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溴乙酸酯处理得到单乙酸酯。用硼氢化钠还原亚胺双键，得到三胺类化合物(1)。类似地，以对取代苯甲醛和二乙烯三胺为起始原料，还原希夫碱，再经胺的羧甲基化得到相应的三乙酸衍生物(2)。此外，水杨醛类化合物与三(2-氨基乙基)胺缩合得到三臂螯合物(3)。目前正在合成这些配合物(1-3)的Gd配合物，并对其磁性进行测试。