Molecular imaging using hyperpolarized carbon-13

使用超极化碳 13 进行分子成像

基本信息

批准号：
7230103
负责人：
STEPHEN J KADLECEK
金额：
$ 14.52万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-18 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7230103
关键词：
Address Aerobic Affect Apoptosis Binding Biochemical Biological Biological Preservation Blood Blood specimen Carbon Carcinoma Cell Line Cell Nucleus Cell Respiration Cell physiology Cells Citric Acid Cycle Class Clinical Treatment Clinical Trials Complex Condition Count Cultured Cells DNA DU145 Detection Diagnosis Diagnostic Discrimination Dose Environment Enzyme Inhibitor Drugs Enzyme Inhibitors Enzyme Interaction Enzymes Equipment Event Frequencies Fumarates Future Gases Gene Expression Genetic Goals Hemoglobin Hepatocyte High temperature of physical object Histone Deacetylase Histone Deacetylase Inhibitor Hydrogenation Image Imagery In Vitro Ion Exchange Isotopes Label Life Location Lung Magnetic Resonance Magnetic Resonance Imaging Magnetism Malignant - descriptor Malignant Neoplasms Malonates Measurement Measures Metabolic Metabolic Pathway Metabolism Methods Modality Modeling Molecular Molecular Probes Molecular Structure NMR Spectroscopy Noble Gases Nuclear Nuclear Decay Numbers Operative Surgical Procedures PC3 cell line Parents Pathway interactions Personal Satisfaction Pharmaceutical Preparations Phenylacetates Phenylbutyrates Physiologic pulse Plasma Pliability Positioning Attribute Principal Investigator Production Property Protein Binding Protons Pulse taking Pyruvate Pyruvates Radioisotopes Rate Rattus Reaction Relaxation Research Research Personnel Resolution Safety Serum Proteins Signal Transduction Sodium Solid Neoplasm Solubility Solutions Solvents Spectrum Analysis Structure Succinates Techniques Technology Temperature Testing Thinking Time Tissues Tracer Uncertainty Variant Work acetoacetyl CoA anaerobic glycolysis anticancer treatment cancer diagnosis catalyst cell motility in vivo inhibitor/antagonist member molecular imaging oncology optical imaging organic acid phenylacetate phenylbutyrate phenylbutyrylglutamine pressure programs prototype response success succinate succinyl-coenzyme A uptake

项目摘要

DESCRIPTION (provided by applicant): Molecular imaging has been defined as "the visualization in space and time of normal and abnormal cellular processes at the level of molecular or genetic function". In this project, we plan to develop a new variety of MRI that utilizes magnetically labeled molecular probes, and demonstrate its use in studies of molecular events with applications to cancer diagnosis and treatment. Associated with this labeling is a signal enhancement of a few orders of magnitude (10 to 105) that increases the sensitivity of 1H-MRI. Furthermore, upon transfer of the initial proton polarization to other nuclei (e.g., 15N, 19F, 31P, or in this case 13C), the corresponding sensitivity increases significantly expand the applicability and utility of emerging hetero-MRI techniques. In particular, events become detectable at much lower concentration, shorter timescale, and with greater spatial resolution. We will take advantage of the Parahydrogen-Induced Polarization phenomenon known from NMR spectroscopy to generate specific hyperpolarized target molecules, chosen for their slow relaxation to the unlabeled state and an unambiguous signaling (through change in resonance frequency) of an important biological event. Preliminary results have demonstrated the feasibility of polarizing 13C in the biologically important class of small organic acids. We propose to extend this work by focusing on 2-succinate and 4-phenylbutyrate. These molecules display favorable relaxation and biological tolerance properties, rapid metabolism, and clear applicability to oncology research and diagnosis. Additionally, despite extensive in vitro and in vivo studies of both compounds, important gaps remain in our current understanding that may be elucidated through application of these techniques. The planned work consists of modifying existing equipment to consistently achieve a high degree of magnetic labeling, and measuring metabolism and other bioactivity in cell cultures. This effort also lays the ground work for planned in vivo studies by measuring magnetic interactions with blood and tissue components. Key Words: Polarized Carbon-13 MRI; Metabolic imaging; Molecular imaging.

描述（由申请人提供）：分子成像被定义为“分子或遗传功能水平上正常和异常细胞过程在空间和时间上的可视化”。在这个项目中，我们计划开发一种利用磁性标记分子探针的新型 MRI，并展示其在分子事件研究以及癌症诊断和治疗中的应用。与此标记相关的是几个数量级（10 至 105）的信号增强，从而提高了 1H-MRI 的灵敏度。此外，当初始质子极化转移到其他原子核（例如 15N、19F、31P 或本例中的 13C）时，相应的灵敏度增加显着扩展了新兴异质 MRI 技术的适用性和实用性。特别是，事件可以在更低的浓度、更短的时间尺度和更高的空间分辨率下被检测到。我们将利用核磁共振波谱中已知的仲氢诱导极化现象来生成特定的超极化目标分子，这些目标分子因其缓慢弛豫至未标记状态以及重要生物事件的明确信号（通过共振频率的变化）而被选择。初步结果证明了在生物学上重要的一类小有机酸中极化 13C 的可行性。我们建议通过关注 2-琥珀酸酯和 4-苯基丁酸酯来扩展这项工作。这些分子表现出良好的松弛和生物耐受特性、快速代谢以及对肿瘤学研究和诊断的明确适用性。此外，尽管对这两种化合物进行了广泛的体外和体内研究，但我们目前的理解仍然存在重要差距，可以通过应用这些技术来阐明。计划的工作包括修改现有设备，以始终如一地实现高度的磁性标记，并测量细胞培养物中的代谢和其他生物活性。这项工作还通过测量与血液和组织成分的磁性相互作用为计划的体内研究奠定了基础。关键词：偏振碳13 MRI；代谢成像；分子成像。