Development of Bio-imaging Probes for Morbidity

发病率生物成像探针的开发

基本信息

批准号：
11794026
负责人：
NAGANO Tetsuo
金额：
$ 6.34万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for University and Society Collaboration
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11794026/
关键词：
probe bio-imaging MRI zincion neurotransfer relaxation fertilization プローグ受精一酸化窒素

项目摘要

The MRI image is based upon the NMR signal from the protons of water, and the Signal intensity depends upon the water concentration and relaxation times. Nowadays, there is great interest in MRI contrast agents, which can improve the resolution of MR images. Gadolinium complexes are widely used as contrast agents for MRI.On the other hand, Zn^<2+> is the second most abundant heavy metal ion after iron in the human body. It is an essential component of many enzymes, transcription factors, and synaptic vesicles in excitatory nerve terminals and is present in serum at a concentration of 〜12 μM (total Zn^<2+>). Recently, Zn^<2+> has been reported to play important roles in regulating synaptic transmission and cell death. Therefore, imaging of chelatable Zn^<2+> in the extra- and intracellular environments or in tissues is of interest. A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as Zn^<2+> sensors. We have designed and synthesized (GdL)^<2->, which contains a DTPA-bisamide moiety. The R_1 relaxivity of (GdL)^<2-> solution decreased monotonically on the addition of Zn^<2+>. Moreover, (GdL)^<2-> showed high selectivity for Zn^<2+> against Ca^<2+> and Mg^<2+>. These complexes should provide the basis for creating a superior Zn^<2+> sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn^<2+> in biological applications.

MRI图像基于水质子的NMR信号，信号强度取决于水的浓度和松弛时间。如今，对MRI对比剂的兴趣非常感兴趣，这可以改善MR图像的分辨率。 Gadolinium复合物被广泛用作MRI的对比剂。另一方面，Zn^<2+>是仅次于人体中铁的第二大重金属离子。它是兴奋性神经末端中许多酶，转录因子和突触蔬菜的重要组成部分，并且在血清中以〜12μM的浓度存在（总Zn^<2+>）。最近，据报道Zn^<2+>在控制合成传播和细胞死亡方面起着重要作用。因此，在细胞外环境或组织中对螯合Zn^<2+>的成像是有意义的。已经准备了一系列新的二乙烯乙乙酸乙酸苯甲酸苯甲酸苯胺丙氨酸乙酸（DTPA） - 二酰胺螯合剂，并将其表征为Zn^<2+>传感器。我们已经设计和合成（GDL）^<2->，其中包含DTPA-BISAMIDE部分。（GDL）^<2->溶液的R_1松弛性在添加Zn^<2+>时单调降低。此外，（gdl）^<2->对Ca^<2+>和mg^<2+>的Zn^<2+>显示出很高的选择性。这些复合物应为创建优质的Zn^<2+>敏感的MRI对比剂提供基础，并且是公司在生物应用中选择性检测Zn^<2+>的传感器的出色候选者。