Responsive Iron MRI probes with Enhanced Relaxivity

具有增强弛豫能力的响应式铁 MRI 探头

• 批准号: 2400128
• 负责人: Janet Morrow
• 金额: $ 55.3万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2400128&HistoricalAwards=false
• 关键词: Responsive; Iron; MRI; probes; Enhanced

With the support of the Chemical Structure, Dynamics & Mechanisms-B (CSDM-B) Program and the Chemical Measurement and Imaging (CMI) program of the Chemistry Division, Professor Janet Morrow and her team in the Department of Chemistry at the University of Buffalo, the State University of New York is developing new classes of magnetic resonance imaging (MRI) contrast agents or probes based on iron coordination complexes. The goal of this research is to design contrast agents that produce a strong MRI signal by using the biologically relevant metal, iron. These iron-based agents will be in the form of small molecule complexes or liposomal nanoparticles. One class of iron-based agents will be stabilized in the signal producing form and the other class will produce signal only under oxidizing conditions of inflammation. The project lies at the nexus of organic, inorganic, biological chemistry and imaging science. Professor Janet Morrow's group is well-positioned to educate and train graduate and undergraduate students including those underrepresented in science. Outreach activities involving high school students and their teachers will be part of the funded project with the goal of developing laboratory and lecture materials on the preparation and magnetic properties of iron nanoparticles. Fe(III)-based MRI probes are of interest as alternatives for Gd(III) complexes used in the clinic and also for the development of responsive contrast agents for the registration of inflammation found in disease states. The proposed research will explore the synthesis of iron-based MRI probes as small molecules or incorporated into liposomal agents and will include studies in solution and in mice. Overall goals include the optimization of Fe(III) coordination complexes as relaxation agents through the study of the magnetic field strength dependence of the longitudinal relaxivity (T1) by using nuclear magnetic relaxation dispersion (NMRD) to gain information on water interactions and electronic relaxation processes. Second, the expertise of Professor Janet Morrow's group in the coordination chemistry of both Fe(II) and Fe(III) places them in a strong position to address the challenges of developing MRI contrast agents that are responsive to oxidation processes corresponding to inflammation. Coordination complexes and liposomal agents will be studied as responsive MRI probes in solution in the presence of enzymes that generate oxidants found in inflammatory processes. Finally, MRI studies in mice will enable the exploration of biodistribution of the probe and provide opportunities for studying inflammation-impacted tissue as a long-term goal.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系化学结构、动力学和机理B(CSDM-B)计划和化学测量和成像(CMI)计划的支持下，纽约州立大学布法罗大学化学系的Janet Morrow教授和她的团队正在开发基于铁配位络合物的新型磁共振成像(MRI)造影剂或探针。这项研究的目标是设计造影剂，通过使用与生物相关的金属铁来产生强烈的MRI信号。这些铁基试剂将以小分子络合物或脂质体纳米颗粒的形式存在。一类铁基试剂将稳定在信号产生形式，而另一类仅在炎症的氧化条件下才会产生信号。该项目涉及有机、无机、生物化学和成像科学。珍妮特·莫罗教授的团队在教育和培训研究生和本科生方面处于有利地位，包括那些在科学界代表性不足的学生。涉及高中生及其教师的外联活动将是资助项目的一部分，目的是开发关于纳米铁的制备和磁性的实验室和讲座材料。基于Fe(III)的MRI探针是临床上使用的Gd(III)络合物的替代品，也是用于注册疾病状态中发现的炎症的响应性造影剂的开发。这项拟议的研究将探索以铁为基础的核磁共振探针的合成作为小分子或结合到脂质体中，并将包括在溶液中和在小鼠身上的研究。总体目标包括通过利用核磁弛豫色散(NMRD)研究磁场强度对纵向弛豫度(T1)的依赖关系来优化Fe(III)配位络合物作为弛豫剂，以获得关于水相互作用和电子弛豫过程的信息。其次，珍妮特·莫罗教授的团队在Fe(II)和Fe(III)的配位化学方面的专业知识使他们处于有利地位，可以应对开发对与炎症相对应的氧化过程做出反应的磁共振造影剂的挑战。配位络合物和脂质体将作为具有响应性的MRI探针在溶液中进行研究，这些酶在炎症过程中会产生氧化剂。最后，在小鼠身上进行的MRI研究将能够探索探针的生物分布，并为研究受炎症影响的组织提供机会作为长期目标。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。