Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

Abstract

Abstract : The incidence of renal cell carcinomas (RCCs) has been steadily increasing, in part due to widespread use of cross-sectional imaging. RCCs have a wide range of aggressiveness, which is currently difficult to assess noninvasively. This has resulted in overtreatment of indolent tumors, and possibly under-treatment of aggressive ones. Therefore, there is an unmet clinical need to be able to reliably distinguish renal cancer aggressiveness for optimal triage of therapies. Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) is a new metabolic imaging approach that is capable of interrogating specific enzymatic pathways in real time. Building on our previous work, on immoratalized cells, we aim to interrogate tumor metabolism in more clinically relevant RCC tumor models by employing patient-derived tumor tissues in conjunction with HP MRSI in this work. The patient-derived tumor models, including tissue slices maintained in a bioreactor and orthotopic mouse model, can better recapitulate the heterogeneous range of RCCs and facilitate identification of clinically relevant markers of tumor aggressiveness. During the first year, we have successfully established the in vivo animal model even with low grade tumors and have accomplished bioreactor HP experiments using live patient derived tumor tissue.