New Reagents for DNP Enhanced Metabolic Imaging

用于 DNP 增强代谢成像的新试剂

• 批准号: 8619048
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 21.37万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8619048
• 关键词: Adherent Culture; Animal Model; Attention; Caffeine; Cell Line; Cell Nucleus; Cell surface; Cells; Detection; Development; Diagnostic; Disease; Drug Kinetics; Drug toxicity; Fluorescence; Fructose; Fucose; Fumaric acid; Image; In Vitro; Investigation; Label; Laboratories; Life; MRI Scans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetism; Malignant - descriptor; Malignant Neoplasms; Metabolic; Metabolic Pathway; Metabolism; Methodology; Methods; Mitochondria; Modeling; Modification; Monitor; Nuclear; Organism; Perfusion; Pharmaceutical Preparations; Physiologic pulse; Physiological; Polysaccharides; Protocols documentation; Protons; Pyruvate; Pyruvate Metabolism Pathway; Pyruvic Acid; Reagent; Relaxation; Sialic Acids; Site; Solvents; Staging; Suspension Culture; Suspension substance; Suspensions; System; Technology; Testing; Time; Tissues; Variant; analog; base; cell type; design; disease diagnosis; drug metabolism; improved; in vivo; method development; novel; optical imaging; public health relevance; response; singlet state; tool

PROJECT SUMMARY/ABSTRACT Application of magnetic resonance spectroscopy (MRS) to the real-time monitoring of metabolic processes in living systems has been advanced tremendously by the introduction of dissolution dynamic nuclear polarization (DNP) as a means of improving sensitivity. With this improvement has come the promise of using metabolic signatures in the diagnosis of disease and in the subsequent monitoring of treatment. Because of the need to prolong storage of polarization and maintain good sensitivity, most applications have been based on polarization and direct observation of 13C enriched at carbonyl or carboxyl sites in metabolic precursors such as pyruvic acid. These non-protonated sites have low relaxation rates, and polarization can be stored for several tens of seconds. However, a much broader range of metabolic pathways could be monitored with suitable attention to the use of other magnetic nuclei, to the use of new means of prolonging polarization storage, and to the development of methodology for observation of polarized sites in a broader range of metabolic products. We have recently developed methodology for exchange facilitated indirect detection of deuterated 15N and 13C sites as a means of improving sensitivity and expanding the range of metabolic applications. We propose to now explore potential applications through the synthesis and testing of an expanded set of metabolic precursors. We also propose the synthesis and testing of new reagents capable of prolonged polarization storage in a singlet state. These reagents have potential in both metabolic monitoring and MR imaging . The specific aims include 1) extending polarization storage times of normally protonated 15N and 13C sites in substrates through deuteration and improving detection of products through exchange facilitated indirect detection, 2) synthesizing novel bioorthogonal reagents capable of singlet state storage and monitoring of cell-surface glycan modification, and 3) developing improved apparatus and protocols for in-cell testing of substrates and reagents.

项目摘要/摘要 将磁共振光谱（MRS）应用于代谢过程的实时监测 通过引入溶解动态核极化，生活系统已大大提高 （DNP）作为提高灵敏度的一种手段。随着这种改进，有望使用代谢 疾病诊断和随后的治疗监测中的特征。因为需要 延长极化并保持良好灵敏度，大多数应用都基于 在代谢前体中富含羧基或羧基位点富含13C的极化和直接观察 作为丙酮酸。这些非转化位点的放松率较低，并且可以存储极化 几十秒。但是，可以监测更广泛的代谢途径 适当注意使用其他磁核的使用，用于延长极化的新方法 存储，以及开发用于观察两极分化位点的方法论 代谢产品。我们最近开发了交换的方法论，以促进间接检测 剥离15N和13C位点，以提高灵敏度并扩大代谢范围 申请。我们现在建议通过合成和测试探索潜在的应用 扩展的一组代谢前体。我们还建议对能够的新试剂的合成和测试 长时间的极化存储在单线状态下。这些试剂在两种代谢监测中都有潜力 和先生成像。具体目的包括1）延长正态质子化15N的极化存储时间 和通过交换来改善产品的底物中的13C位点 促进间接检测，2）合成能够单线储存和的新型生物正交试剂 监测细胞表面聚糖的修饰，3）开发改进的设备和协议 测试底物和试剂。