Molecular imaging using hyperpolarized carbon-13

描述（由申请人提供）：分子成像已被定义为“在分子或遗传功能水平上对正常和异常细胞过程进行空间和时间可视化”。在这个项目中，我们计划开发一种新的MRI，利用磁性标记的分子探针，并证明其在分子事件研究中的用途，并应用于癌症的诊断和治疗。与这种标记相关的是几个数量级（10至105）的信号增强，这增加了1H-MRI的灵敏度。此外，在初始质子极化转移到其他核（例如，15 N、19 F、31 P或在这种情况下为13 C），相应的灵敏度增加显著扩展了新兴的异质MRI技术的适用性和实用性。特别是，事件在低得多的浓度、更短的时间尺度和更高的空间分辨率下变得可检测。我们将利用从NMR光谱学已知的仲氢诱导极化现象来产生特定的超极化靶分子，选择它们缓慢弛豫到未标记状态和明确的信号（通过共振频率的变化）的重要生物事件。初步结果表明，极化13 C的生物重要类的小有机酸的可行性。我们建议通过专注于2-琥珀酸和4-苯基丁酸来扩展这项工作。这些分子显示出良好的松弛和生物耐受性，快速代谢，并明确适用于肿瘤学研究和诊断。此外，尽管这两种化合物的广泛的体外和体内研究，重要的差距仍然存在于我们目前的理解，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。这项工作也奠定了基础工作计划在体内研究，通过测量磁相互作用与血液和组织成分。关键词：极化碳-13磁共振成像;代谢成像;分子成像。

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.