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.

项目总结/摘要 应用磁共振波谱（MRS）实时监测代谢过程， 由于溶解动力学核极化的引入，生命系统得到了极大的发展 (DNP)作为提高灵敏度的一种手段。随着这一改进，使用代谢的希望已经到来。 在疾病诊断和随后的治疗监测中的签名。因为需要 延长偏振的存储时间并保持良好的灵敏度，大多数应用都是基于 极化和直接观察在代谢前体中的羰基或羧基位点富集的13 C， 作为维生素A酸。这些非质子化位点具有低的弛豫速率，并且极化可以被存储用于 几十秒。然而，更广泛的代谢途径可以监测与 适当注意使用其他磁核，注意使用新的延长极化的手段 储存，并制定方法，在更广泛的范围内观察极化网站， 代谢产物我们最近开发了交换促进的间接检测方法， 氘代15 N和13 C位点作为提高灵敏度和扩大代谢范围的手段 应用.我们建议现在通过合成和测试一种 代谢前体的扩展集合。我们还提出了新试剂的合成和测试， 在单重态中的延长的极化存储。这些试剂在代谢监测和 和磁共振成像。具体目标包括：1）延长正常质子化15 N的极化存储时间 和13 C位点，并通过交换改善产物的检测 促进间接检测，2）合成能够单重态储存的新型生物正交试剂， 监测细胞表面聚糖修饰，以及3）开发改进的细胞内设备和方案 底物和试剂的测试。