IGF::OT::IGF SBIR PHASE I TOPIC 350 QUANTIFICATION OF REDOX

IGF::OT::IGF SBIR 第一阶段主题 350 氧化还原定量

• 批准号: 9364364
• 负责人: JOSEPH WALISH
• 金额: $ 22.5万
• 依托单位: DYNUPOL, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2017-06-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9364364
• 关键词: 2,4-Dinitrophenol; Bioreactors; Cells; Clinical; Dehydroascorbic Acid; Diabetes Mellitus; Disease; Electrons; Exhibits; Free Radicals; Frequencies; Image; Imaging Techniques; Kidney; Label; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metabolic; Nuclear; Oxidation-Reduction; Oxidative Stress; Patients; Phase; Preparation; Problem Solving; Procedures; Pyruvate; Reactive Oxygen Species; Reagent; Relaxation; Resolution; Small Business Innovation Research Grant; Solvents; Testing; Time; Translations; United States National Institutes of Health; base; cancer cell; cost; dehydroascorbate; ethylene glycol; improved; meetings; microwave electromagnetic radiation; performance tests; preclinical study; research study; response; serinol; solid state; spatiotemporal

Current clinical magnetic resonance metabolic imaging techniques are severely hindered by poor sensitivity. Dynamic nuclear polarization solves this problem by transferring polarization from the highly-polarized electron spins of a polarization agent to the nuclear spins of the target MRI probe. The metabolite dehydroascorbic acid (DHA) has been shown to be an excellent hyperpolarized probe of cellular redox capacity providing a measure of the cells ability to quench reactive oxygen species (ROS). Pre-clinical studies have demonstrated hyperpolarized DHA's ability to measure increased reducing capacity in cancer and diabetes-induced renal oxidative stress and their response to therapy, and it’s anticipated to have broad applicability to a variety of diseases. With the successful clinical translation of 13C MRI of hyper polarized [1-13C] pyruvate, the use of HP [1-13C]DHA in patients is being actively pursued. However, the spatiotemporal resolution of HP [1-13C]DHA is severely hampered by the relatively poor polarization that is being obtained using the current trityl-based polarization radicals. Additionally, broad use of HP DHA is limited by the high cost of the trityl radicals. A Phase I effort will focus on increasing DHA’s polarization by 2-fold with Dynupol’s polarization agents, enabling higher resolution and sensitivity in cellular-redox imaging of a variety of diseases.

目前的临床磁共振代谢成像技术因灵敏度差而受到严重阻碍，动态核极化通过将极化剂的高极化电子自旋转移到目标 MRI 探针的核自旋来解决这个问题。一种出色的细胞氧化还原能力超极化探针，可测量细胞淬灭活性氧 (ROS) 的能力。临床前研究已证明。超极化 DHA 能够测量癌症和糖尿病引起的肾脏氧化应激的增强还原能力及其对治疗的反应，随着超极化 13C MRI 的成功临床转化，预计它对多种疾病具有广泛的适用性。 13C]丙酮酸，正在积极寻求在患者中使用 HP [1-13C]DHA 然而，HP [1-13C]DHA 的时空分辨率尚不清楚。由于目前使用的严重三苯甲基自由基获得的极化相对较差，因此 HP DHA 的广泛使用受到三苯甲基自由基成本高的限制，第一阶段的努力将集中于将 DHA 的极化提高 2。 - 折叠 Dynupol 的偏振剂可在多种疾病的细胞氧化还原成像中实现更高的分辨率和灵敏度。