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严重阻碍了灵敏度差。动态核极化通过将极化剂的高极化电子自旋的极化转移到目标MRI探针的核自旋来解决这一问题。代谢产物脱氢抗坏血酸（DHA）已被证明是细胞氧化还原能力的极好超极化探针，提供了细胞抑制活性氧（ROS）能力的测量。临床前研究已经证明，超极化DHA能够测量癌症和糖尿病诱导的肾脏氧化应激增加的还原能力及其对治疗的反应，预计它将广泛适用于各种疾病。随着超极化[1-13C]丙酮酸的13C MRI临床翻译的成功，HP [1-13C]DHA在患者中的应用正在积极寻求。然而，HP [1-13C]DHA的时空分辨率受到当前基于三烷基的极化自由基相对较差的极化的严重影响。此外，三烷基自由基的高成本限制了HP DHA的广泛使用。第一阶段的工作将侧重于将DHA的极化率提高两倍