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、动力学与机理-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Janet Morrow教授及其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。这项研究的目标是设计利用生物相关金属铁产生强 MRI 信号的造影剂。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，另一类仅在炎症氧化条件下产生信号。该项目结合了有机、无机、生物化学和成像科学。 珍妮特·莫罗教授的团队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。 涉及高中生及其教师的外展活动将成为资助项目的一部分，其目标是开发有关铁纳米颗粒的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) 复合物的替代品以及用于开发用于记录疾病状态中发现的炎症的响应性造影剂而引起人们的兴趣。拟议的研究将探索以小分子形式合成铁基 MRI 探针或将其纳入脂质体制剂中，并将包括在溶液中和小鼠中的研究。总体目标包括通过研究纵向弛豫率 (T1) 的磁场强度依赖性，通过使用核磁弛豫色散 (NMRD) 获取有关水相互作用和电子弛豫过程的信息，优化 Fe(III) 配位络合物作为弛豫剂。其次，Janet Morrow 教授团队在 Fe(II) 和 Fe(III) 配位化学方面的专业知识使他们在应对开发 MRI 造影剂的挑战方面处于有利地位，这些造影剂对炎症对应的氧化过程敏感。配位复合物和脂质体制剂将在酶存在的情况下作为溶液中的响应性 MRI 探针进行研究，这些酶会产生炎症过程中发现的氧化剂。 最后，小鼠 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作为长期目标提供机会。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力评估进行评估，被认为值得支持。优点和更广泛的影响审查标准。