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New Reagents for DNP Enhanced Metabolic Imaging

用于 DNP 增强代谢成像的新试剂

基本信息

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
项目类别：
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

项目摘要

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/文摘