Transition metal PARACEST MRI contrast agents: Fe(II), Ni(II), Co(II)

在化学测量和成像项目的支持下，纽约州立大学布法罗分校的Janet Morrow教授及其团队正在开发利用生物相关金属离子Fe（II）、Co（II）和Ni（II）的新型磁共振成像（MRI）造影剂。 这些过渡金属离子的配位络合物通过顺磁化学交换饱和转移（PARACEST）产生对比度。 主要目标是设计具有远离本体水（100 ppm）的可交换质子共振的PARACEST试剂，并优化交换速率常数以增强对比度。 第二，过渡金属元素的不同氧化态的广泛配位化学和可及性促进了对生物环境响应的造影剂的设计。 例如，将制备通过pH或氧化还原电位的变化而开启的PARACEST试剂。 将在4.7 T扫描仪上进行CEST NMR实验和CEST MRI实验，目的是开发成像方案以优化对比度。 将为本科生和高中教师及其学生开发实验，以建立金属离子的磁特性与MR成像之间的联系。 MRI是临床上重要的诊断程序，大约一半的MRI扫描使用造影剂，以便更好地成像组织中的差异。 在具有疾病状态特征的组织中开启的造影剂的开发对于改进的诊断和治疗可能是非常有用的。 拟议的研究将集中在开发这种含有铁、钴或镍的可转换造影剂上。 这些金属离子，特别是铁，可能比目前使用的稀土造影剂更安全，因为它们可以代谢再循环。 该项目将开发必要的配位化学和成像协议，以挖掘这些新造影剂在成像应用中的重要和未开发的潜力。

With support from the Chemical Measurement and Imaging Program, Prof. Janet Morrow and her group at the University at Buffalo, State University of New York are developing new magnetic resonance imaging (MRI) contrast agents that utilize the biologically relevant metal ions, Fe(II), Co(II) and Ni(II). Coordination complexes of these transition metal ions produce contrast through paramagnetic chemical exchange saturation transfer (PARACEST). The primary goal is to design PARACEST agents with exchangeable proton resonances shifted far from those of bulk water ( 100 ppm) and to optimize exchange rate constants for enhanced contrast. Second, the extensive coordination chemistry and accessibility of different oxidation states of transition metal elements facilitates the design of contrast agents that are responsive to biological environment. For example, PARACEST agents that are switched on by a change in pH or redox potential will be prepared. CEST NMR experiments and CEST MRI experiments on a 4.7 T scanner will be conducted with the goal of developing imaging protocols for optimizing contrast. Experiments for undergraduates and high school teachers and their students will be developed to make the connection between magnetic properties of metal ions and MR imaging. MRI is a clinically important diagnostic procedure, with about half of MRI scans using contrast agents in order to better image differences in tissue. The development of contrast agents that switch on in tissue which has characteristics of a disease state could be extremely useful for improved diagnostics and treatment. The proposed research will focus on the development of such switchable contrast agents that contain iron, cobalt or nickel. These metal ions, especially iron, may be potentially safer than currently utilized rare earth contrast agents because they may be metabolically recycled. This project will develop the coordination chemistry and imaging protocols that are necessary to tap into the significant and unexplored potential of these new contrast agents for imaging applications.