Iron(III) Coordination Complexes as MRI Contrast Agents

铁 (III) 配位络合物作为 MRI 造影剂

• 批准号: 1710224
• 负责人: Janet Morrow
• 金额: $ 48.94万
• 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: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710224&HistoricalAwards=false
• 关键词: Iron; III; Coordination; Complexes; MRI

In this project funded by the Chemical Structure, Dynamic & Mechanism B and the Chemical Measurement & Imaging Programs of the Chemistry Division, Professor Janet R. Morrow of the Department of Chemistry at the University at Buffalo, State University of New York is developing new classes of iron (Fe) complexes as magnetic resonance imaging (MRI) contrast agents. The goal of this research is to obtain new iron-based agents that produce effective MRI contrast at the field strengths found in the newest MRI scanners. Iron is a biologically relevant metal ion that may be an alternative to the currently used gadolinium, which has tolerance issues in imaging. The project lies at the interface of organic and inorganic chemistry, as well as physiology and imaging physics and is therefore well suited to the education of scientists at all levels. Professor Morrow has a strong record of educating a diverse group of graduate and undergraduate students. Outreach activities involving K-12 students and their science teacher are also be part of the funded project. Macrocyclic Fe(III) complexes are being developed as MRI contrast agents with the goal of obtaining agents that produce effective T1 contrast at the clinically relevant magnetic field of 3 Tesla (T). The complexes contain highly stabilized Fe(III) centers that do not produce reactive oxygen species. Complexes that contain one bound water or no water ligands are to be studied to assess the effect of outer versus innersphere water on T1 relaxivity. A second emphasis is to develop Fe(III) contrast agents that change paramagnetic properties with temperature and pH. These spin state changes interconvert Fe(III) paramagnetic CEST (Chemical Exchange Saturation Transfer) agents and T1 contrast agents. EPR (Electron paramagnetic resonance) and Mossbauer spectroscopy will be used for characterization of the complexes. To study the magnetic field strength dependence of relaxivity, the complexes will be studied on MRI scanners at 1.5 T, 3.0 T and 4.7 T. A nuclear magnetic resonance dispersion spectrum will be obtained for selected Fe(III) complexes. The most effective Fe(III) contrast agents will be studied and compared to Gd(III) contrast agents in biological samples.

在这个由化学系化学结构、动力学和机理 B 以及化学测量和成像项目资助的项目中，纽约州立大学布法罗分校化学系的 Janet R. Morrow 教授正在开发新课程铁（Fe）络合物作为磁共振成像（MRI）造影剂。 这项研究的目标是获得新的铁基试剂，在最新 MRI 扫描仪的场强下产生有效的 MRI 对比度。 铁是一种与生物相关的金属离子，可能是目前使用的钆的替代品，钆在成像方面存在耐受性问题。 该项目位于有机和无机化学以及生理学和成像物理学的交汇处，因此非常适合各级科学家的教育。 莫罗教授在教育多元化的研究生和本科生方面拥有良好的记录。 涉及 K-12 学生及其科学老师的外展活动也是该资助项目的一部分。 大环 Fe(III) 配合物正在开发作为 MRI 造影剂，目标是获得在 3 特斯拉 (T) 临床相关磁场下产生有效 T1 造影剂的试剂。该配合物含有高度稳定的 Fe(III) 中心，不会产生活性氧。 将研究含有一个结合水或不含水配体的配合物，以评估外层水与内层水对 T1 弛豫率的影响。 第二个重点是开发随温度和 pH 值改变顺磁性的 Fe(III) 造影剂。 这些自旋状态的变化使 Fe(III) 顺磁性 CEST（化学交换饱和转移）试剂和 T1 造影剂相互转化。 EPR（电子顺磁共振）和穆斯堡尔光谱将用于表征配合物。为了研究弛豫率对磁场强度的依赖性，将在 1.5 T、3.0 T 和 4.7 T 的 MRI 扫描仪上研究配合物。将获得选定 Fe(III) 配合物的核磁共振色散谱。 将研究最有效的 Fe(III) 造影剂，并将其与生物样品中的 Gd(III) 造影剂进行比较。

项目成果

An Fe III Azamacrocyclic Complex as a pH-Tunable Catholyte and Anolyte for Redox-Flow Battery Applications

Fe III 氮杂大环配合物作为氧化还原液流电池应用中 pH 可调的阴极电解液和阳极电解液

• DOI: 10.1002/chem.201704381
• 发表时间: 2017-11
• 期刊: Chemistry - A European Journal
• 作者: Tsitovich, Pavel B.;Kosswattaarachchi, Anjula M.;Crawley, Matthew R.;Tittiris, Timothy Y.;Cook, Timothy R.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.

Saccharomyces cerevisiae and Candida albicans Yeast Cells Labeled with Fe(III) Complexes as MRI Probes

用 Fe(III) 复合物标记的酿酒酵母和白色念珠菌酵母细胞作为 MRI 探针

• DOI: 10.3390/magnetochemistry6030041
• 发表时间: 2020-09
• 期刊: Magnetochemistry
• 影响因子: 2.7
• 作者: Patel, Akanksha;Asik, Didar;Snyder, Eric M.;Spernyak, Joseph A.;Cullen, Paul J.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.

Binding and Release of FeIII Complexes from Glucan Particles for the Delivery of T 1 MRI Contrast Agents

用于 T 1 MRI 造影剂输送的葡聚糖颗粒中 FeIII 复合物的结合和释放

• DOI: 10.1002/cmdc.202000003
• 发表时间: 2020-04
• 期刊: ChemMedChem
• 影响因子: 3.4
• 作者: Patel, Akanksha;Asik, Didar;Snyder, Eric M.;Dilillo, Alexandra E.;Cullen, Paul J.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.

MRI and fluorescence studies of Saccharomyces cerevisiae loaded with a bimodal Fe(III) T1 contrast agent

负载双峰 Fe(III) T1 造影剂的酿酒酵母的 MRI 和荧光研究

• DOI: 10.1016/j.jinorgbio.2019.110832
• 发表时间: 2019-12
• 期刊: Journal of Inorganic Biochemistry
• 影响因子: 3.9
• 作者: Patel, Akanksha;Asik, Didar;Spernyak, Joseph A.;Cullen, Paul J.;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.

Exploring Inner-Sphere Water Interactions of Fe(II) and Co(II) Complexes of 12-Membered Macrocycles To Develop CEST MRI Probes

探索 12 元大环 Fe(II) 和 Co(II) 配合物的内层水相互作用以开发 CEST MRI 探针

• DOI: 10.1021/acs.inorgchem.9b01072
• 发表时间: 2019-06
• 期刊: Inorganic Chemistry
• 影响因子: 4.6
• 作者: Bond, Christopher J.;Sokolow, Gregory E.;Crawley, Matthew R.;Burns, Patrick J.;Cox, Jordan M.;Mayilmurugan, Ramasamy;Morrow, Janet R.
• 通讯作者: Morrow, Janet R.