Responsive Iron MRI probes with Enhanced Relaxivity

在化学系的化学结构、动力学机制-B（CSDM-B）项目和化学测量与成像（CMI）项目的支持下，布法罗大学化学系的Janet Morrow教授和她的团队，纽约州立大学正在开发基于铁配位复合物的新型磁共振成像（MRI）造影剂或探针。本研究的目的是设计造影剂，通过使用生物相关的金属，铁产生强MRI信号。这些铁基试剂将呈小分子复合物或脂质体纳米颗粒的形式。 一类铁基试剂将以信号产生形式稳定，另一类仅在炎症的氧化条件下产生信号。该项目是有机，无机，生物化学和成像科学的联系。 珍妮特·莫罗教授的小组有能力教育和培训研究生和本科生，包括那些在科学领域代表性不足的学生。 涉及高中学生及其教师的外联活动将是资助项目的一部分，其目标是开发关于铁纳米颗粒制备和磁性的实验室和讲座材料。基于Fe（III）的MRI探针作为临床中使用的Gd（III）络合物的替代物以及用于开发用于登记疾病状态中发现的炎症的响应性造影剂是令人感兴趣的。拟议的研究将探索铁基MRI探针作为小分子或掺入脂质体制剂的合成，并将包括在溶液和小鼠中的研究。总体目标包括优化Fe（III）配位络合物作为弛豫剂，通过研究磁场强度对纵向弛豫率（T1）的依赖性，利用核磁弛豫色散（NMRD）获得水相互作用和电子弛豫过程的信息。其次，Janet Morrow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，以应对开发对炎症相应的氧化过程有反应的MRI造影剂的挑战。配合物和脂质体制剂将作为响应MRI探针在溶液中的酶，产生氧化剂的存在下，发现在炎症过程中进行研究。 最后，在小鼠中进行的MRI研究将有助于探索探针的生物分布，并为研究炎症影响的组织提供机会，作为长期目标。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.