Molecular imaging using hyperpolarized carbon-13

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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.