MOLECULAR ASPECTS OF MRI CONTRAST AGENTS SELECTIVITY

增强磁共振成像(MRI)是一种非常有效的 临床诊断技术。然而，大多数顺磁性造影剂 (PCA)纯基于非特定生物的图像对比度增强 分布属性，这有时足以可视化一些 生化事件。目前，对这一问题的认识还存在一些空白 PCA的构效关系及可逆的分子机制 PCA与生物小分子的结合及生物效应 环境对主成分分析松弛的影响。拟议方案的总体目标 项目是了解分子方面的结合和相互作用 为临床MRI应用开发的PCA分子具有几个关键 生物分子，如血浆蛋白和磷脂，以及 束缚与松弛增强之间的关系。目标将是 通过表征结合相互作用和通过研究 这些相互作用对化合物结构和电子性质的影响 几类Gd3+络合物的主成分分析 各种光谱技术，包括荧光、核 磁共振和电子顺磁共振在多个和 频率很高。这一关键信息对指导发展至关重要 新的，更有效的造影剂，具有增强的松弛能力和 选择性。

Contrast-enhanced magnetic resonance imaging (MRI) is a very effective clinical diagnostic technique. However, most paramagnetic contrast agents (PCA) enhance image contrast purely on the basis of nonspecific bio- distribution properties, which is sometimes enough to visualize some biochemical events. Currently, there are some gaps in understanding of the structure-function relationship of PCA, molecular mechanism of reversible binding of PCA to biological micromolecules, and the effect of biological environment on relaxivity of PCA. The broad objectives of the proposed project are to understand molecular aspects of binding and interactions of PCA molecules developed for clinical MRI applications with several key biomolecules, such as plasma proteins and phospholipids, and the relationship between binding and relaxation enhancement. The goal will be achieved by characterization of binding interaction and by investigating effects of these interactions on structure and electronic properties of PCA's through systematic study of several classes Gd3+ complexes by a variety of spectroscopic techniques, including fluorescence, nuclear magnetic resonance, and electron paramagnetic resonance at multiple and high frequencies. This key information is essential to guide development of new, more effective contrast agents with enhanced relaxivity and selectivity.