Molecular imaging using hyperpolarized carbon-13

描述（由申请人提供）：分子成像被定义为“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中的应用，以及在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到105）的信号增强，增加了1H-MRI的灵敏度。此外，当初始质子极化转移到其他核（如15N、19F、31P或本例中的13C）时，相应的灵敏度显著提高，扩大了新兴的异源磁共振成像技术的适用性和实用性。特别是，在更低的浓度、更短的时间尺度和更高的空间分辨率下，事件变得可检测。我们将利用从核磁共振波谱中已知的对氢诱导极化现象来产生特定的超极化靶分子，选择这些靶分子是因为它们缓慢弛豫到未标记状态，并且是重要生物事件的明确信号（通过共振频率的变化）。初步结果证明了在生物上重要的一类小有机酸中极化13C的可行性。我们建议通过重点研究2-琥珀酸盐和4-苯基丁酸盐来扩展这项工作。这些分子表现出良好的松弛和生物耐受性，代谢迅速，在肿瘤研究和诊断中具有明确的适用性。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的空白，可以通过这些技术的应用来阐明。计划的工作包括修改现有设备，以始终如一地实现高水平的磁性标记，并测量细胞培养中的代谢和其他生物活性。这项工作也为计划中的体内研究奠定了基础，通过测量磁性与血液和组织成分的相互作用。关键词：极化碳-13 MRI；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.