This proposed exploratory/development project is focused on developing and applying new hyperpolarized 13C MR techniques for liver cancer studies. This extraordinary new technique has the potential to become a major new MR metabolic imaging technique by directly observing key cellular bioenergetic processes in vivo by MR. Hyperpolarized 13C imaging provides a >10,000 fold signal enhancement for detecting 13C probes of endogenous, nontoxic substances such as pyruvate to monitor metabolic fluxes through multiple key biochemical pathways (glycolysis, citric acid cycle and fatty acid synthesis). Recent studies of injected 13C labeled substrates, pre-polarized via dynamic nuclear polarization, have demonstrated unprecedented 13C MR signal enhancement and the ability to not only observe uptake but also metabolism in vivo. Our preliminary results using DNP polarizers developed by GE and Oxford Instruments have shown the feasibility to acquire 3D metabolic imaging of preclinical mouse models of liver cancer at high spatial resolution (0.034cm3) and high SNR for not only the hyperpolarized pyruvate, but also the metabolic products of lactate and alanine in only 15 seconds. Prior hyperpolarized 13C studies have shown significant metabolic differences between prostate cancers and normal tissues and also with disease progression and response to therapy. Since the prostate cancer studies have been highly successful, this powerful new metabolic imaging method would presumably be valuable for other cancer types as well. Our clinical colleagues have identified liver cancer as an important application where hyperpolarized MR imaging could have a major medical impact. The goal of this exploratory/development project is to develop and apply hyperpolarized 13C MR to study transgenic models of liver cancer. This multidisciplinary project combines expertise in imaging science, liver cancer research, cancer treatment and radiology to develop and apply specialized hyperpolarized MR techniques for the study of normal liver 13C metabolism and initial liver cancer experiments. This developmental project will focus on transgenic animal model studies to establish feasibility and acquire preliminary metabolic data on liver cancer progression and response to oncogene inhibition.
The successful outcome of the proposed project will advance the development of a new metabolic imaging method, hyperpolarized 13C MRI, for liver cancer studies. This research effort aims to improve our understanding of cancer metabolism and the cellular metabolic response to gene-based therapies.
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