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.

在化学测量和成像计划的支持下，珍妮特·莫罗（Janet Morrow）和她在布法罗大学的小组纽约州立大学正在开发使用新的磁共振成像（MRI）对比剂，这些对比剂利用了生物学相关的金属离子，FE（II），CO（II），CO（II）和Ni（II）。 这些过渡金属离子的配位复合物通过顺磁化学交换饱和转移（Paracest）产生对比度。 主要的目标是设计具有可交换质子共振的最偏执剂与散装水（100 ppm）的变化很远，并优化了汇率常数以增强对比度。 其次，过渡金属元件的不同氧化状态的广泛协调化学和可及性促进了对生物环境响应的对比剂的设计。 例如，将准备通过pH或氧化还原电位变化来打开的最有偏的药物。 将进行4.7 T扫描仪的CEST NMR实验和CEST MRI实验，目的是开发成像协议以优化对比度。 将开发针对本科生和高中教师及其学生的实验，以建立金属离子和MR成像的磁性特性之间的联系。 MRI是一种临床上重要的诊断程序，使用造影剂的MRI扫描中有大约一半，以便更好地图像组织的图像差异。 在具有疾病状态特征的组织中开启的对比剂的发展对于改善诊断和治疗非常有用。 拟议的研究将着重于这种可切换对比剂的开发，这些可切换造影剂包含铁，钴或镍。 这些金属离子，尤其是铁，可能比目前利用的稀土对比剂更安全，因为它们可能是代谢回收的​​。 该项目将开发协调化学和成像协议，这些方案是利用这些新的对比剂对成像应用的重要且未开发的潜力所必需的。