基于钆络合物的MRI/荧光双模式氟离子探针的合成与性能研究

项目名称： 基于钆络合物的MRI/荧光双模式氟离子探针的合成与性能研究

项目编号： No.21301011

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 孟庆涛

作者单位： 辽宁科技大学

项目金额： 24万元

中文摘要： 鉴于氟的重要生理作用以及过量摄入对人体健康造成的巨大危害，在荧光探针法检测氟离子工作的基础上，开展高质量的活体内氟离子分布成像技术的研究，将在生命科学和医学等领域具有重要的理论意义和应用价值。本项目在造影剂Gd-DO3A上引入特定荧光基团，构筑了一系列新型的MRI/荧光双模式氟离子探针。探针分子中的Gd3+不仅是氟离子的键合位点，还是MRI信号输出单元。通过恰当调节探针的结构，当氟离子与Gd3+中心作用后，通过竞争作用，取代配位的一个水分子，同步引起Gd-DO3A单元弛豫速率的改变和荧光团内电子的迁移，从而实现对氟离子的检测和MRI/荧光双模式成像。通过MRI/荧光双模式成像技术获取的氟离子在活体内的分布影像具有灵敏度高、分辨率强的特点，而且这类成像试剂可有效去除活体内相关分子、离子的干扰，专一性强。本课题的研究将为地方性氟中毒的预防、诊疗及其发病机理分析等提供详细可靠的影像学信息。

中文关键词： 氟离子；Gd(Ⅲ)配合物；分子探针；双模式；成像

英文摘要： Fluorine element plays an important role in the life process, but will be a serious health risk once excessive intake. Accordingly, the study of rapid detection methods in water and rhigh-quality imaging techniques in vivo for fluoride will providing great theoretic meaning as well as promising application value in the life and medical fields. In this project, a series of MRI/fluorescence dual-mode fluoride probes were designed and synthetized by the introduction of fluorophores into Gd-DO3A moiety. In these probes, Gd3+ center plays not only a bonding site for fluoride but also a MRI output signal unit. One water molecule coordinated to Gd3+ could be selectively replaced by fluoride in the optimum probe molecule. Therefore, the relaxation rate of Gd-DO3A will be changed and an electronic transfer process also occurred spontaneously within the fluorophores in the process of the displacement reaction, realizing the detection and imaging applications of fluoride by MRI/fluorescence methods. A large amount of imaging information with excellent sensitivity, good selectivity and high resolution will be also achieved by combining the fluorescence method with MRI imaging technique, which could be potentially applied in the prevention, diagnosis, treatment and pathogenesis analysis of endemic fluorosis.

英文关键词： Fluoride；Gd(Ⅲ) complex；Molecular probe；Dual-mode；Imaging