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

过渡金属 PARACEST MRI 造影剂：Fe(II)、Ni(II)、Co(II)

• 批准号: 1310374
• 负责人: Janet Morrow
• 金额: $ 46.5万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1310374&HistoricalAwards=false
• 关键词: Transition; metal; PARACEST; MRI; contrast

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.

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 教授和她的团队正在开发利用生物相关金属离子 Fe(II) 的新型磁共振成像 (MRI) 造影剂)、Co(II) 和 Ni(II)。 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 PARACEST 试剂，其可交换质子共振远离散装水 (100 ppm)，并优化交换速率常数以增强对比度。 其次，过渡金属元素的广泛配位化学和不同氧化态的可及性有利于设计对生物环境敏感的造影剂。 例如，将制备通过pH或氧化还原电位的变化而开启的PARACEST药剂。 将在 4.7 T 扫描仪上进行 CEST NMR 实验和 CEST MRI 实验，目的是开发优化对比度的成像协议。 将为本科生和高中教师及其学生开展实验，以将金属离子的磁性与磁共振成像联系起来。 MRI 是一种临床上重要的诊断程序，大约一半的 MRI 扫描使用造影剂，以便更好地对组织中的差异进行成像。 开发在具有疾病状态特征的组织中启动的造影剂对于改进诊断和治疗非常有用。 拟议的研究将集中于开发此类含有铁、钴或镍的可切换造影剂。 这些金属离子，尤其是铁，可能比目前使用的稀土造影剂更安全，因为它们可以代谢回收。 该项目将开发配位化学和成像方案，以挖掘这些新型造影剂在成像应用方面的巨大且尚未开发的潜力。