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低而受到严重阻碍。动态核极化通过将极化从极化剂的高度极化的电子自旋转移到目标MRI探针的核自旋来解决这个问题。代谢物脱氢抗坏血酸(DHA)已被证明是细胞氧化还原能力的一个极好的超极化探针，提供了一个衡量细胞淬灭活性氧物种(ROS)能力的指标。临床前研究表明，超极化DHA能够测量癌症和糖尿病引起的肾脏氧化应激中还原能力的增加及其对治疗的反应，预计它将广泛适用于各种疾病。随着超极化[1-13C]丙酮酸13C磁共振成像在临床上的成功翻译，HP[1-13C]DHA在患者中的应用正在积极进行中。然而，HP[1-13C]DHA的时空分辨率严重受制于目前使用基于三叔丁基的极化自由基获得的相对较差的极化。此外，HP DHA的广泛使用受到三苯基自由基高成本的限制。第一阶段的工作将集中于将DHA的极化增加2倍， 在多种疾病的细胞氧化还原成像中，可实现更高的分辨率和灵敏度。