Development of Bio-imaging Probes for Morbidity

核磁共振成像是基于水质子的核磁共振信号，信号强度取决于水的浓度和弛豫时间。MRI造影剂可以提高MRI图像的分辨率，是目前研究的热点。钆配合物被广泛用作MRI造影剂。另一方面，Zn^<2+>是人体中含量仅次于铁的第二丰富的重金属离子。它是兴奋性神经末梢许多酶、转录因子和突触囊泡的重要组成部分，在血清中以~ 12 μM（总Zn^<2+>）的浓度存在。最近有报道称Zn^<2+>在调节突触传递和细胞死亡中起重要作用。因此，在细胞外和细胞内环境或组织中螯合Zn^<2+>的成像是有意义的。制备了一系列新型二乙基三胺五乙酸(DTPA)-双酰胺螯合剂，并对其进行了表征，用于Zn^<2+>传感器。我们设计并合成了（GdL）^<2->，它含有dtpa -双酰胺部分。（GdL）^<2->溶液的R_1弛豫度随Zn^<2+>的加入而单调减小。此外，（GdL）^<2->对Zn^<2+>对Ca^<2+>和Mg^<2+>表现出较高的选择性。这些配合物应该为创造一种优良的Zn^<2+>敏感的MRI造影剂提供基础，并且是用于在生物应用中选择性检测Zn^<2+>的传感器的优秀候选者。

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.