The goal of this project is to develop a new method for hyperpolarized (HP) 13C MR imaging and spectroscopy of liver tumors that permits targeted evaluation of tumor metabolism. Metabolic imaging of liver tumors is clinically important for several reasons. Liver tumors are often treated with local-regional therapies (radiation, chemical or thermal ablation), requiring close evaluation for tumor response and recurrence. Additionally, metabolic changes are known to precede size changes following many treatments, especially radiotherapy. HP 13C MRI is a promising emerging molecular imaging tool for with numerous potential applications to cancer imaging including liver tumors. However, the hyperpolarized MR signal is not specific for organ and tissue type. In the injured liver, for example, it is currently impossible to determine if the observed hyperpolarized signal comes from hepatocytes or from inflammatory cells. Similarly, because of the limited spatial resolution of most HP MRI studies, it is likewise impossible to separate the signal arising from small tumors from surrounding non-tumorous hepatocytes, which also have high metabolic activity. This lack of specificity limits the potential for HP 13C MRI to monitor the viability of liver tumors and their responses to treatment. There is therefore an unmet need to increase the cellular specificity of hyperpolarized 13C MRI measurements of liver tumors. We propose to target hyperpolarized 13C MRI to liver tumors by combining hyperpolarized 13C MRI with a liver- specific gadolinium-based contrast agent that is selectively taken into liver cells. Because the agent is located within liver cells but not tumor cells, it will shorten the T1 (and therefore quench the signal) from hyperpolarized compounds located within liver cells and preserve signal arising from tumor cells (which exclude the gadolinium contrast agent). This exploratory study is intended to test and demonstrate the feasibility of this approach. Using an animal model of metastatic colon cancer, hyperpolarized acquisitions will be performed before and after administration of the gadolinium contrast agent. We will find the dose and timing of contrast injection that maximizes the amount of signal received from liver tumor cells while minimizing the amount of signal received from adjacent normal liver. To our knowledge, this will be the first combination of hyperpolarized 13C imaging with gadolinium contrast agents targeted to a particular cell type. In addition, the suppression of background liver signal is not possible using competing molecular imaging technologies such as FDG-PET, which suggests this technology may create a unique role for hyperpolarized 13C MRI in liver tumor imaging. Finally, if this work is successful, this technology should be rapidly translatable to future studies in humans.
This project seeks to improve molecular imaging of liver tumors. This improvement is achieved by blocking the signal arising from normal liver, leaving on the signal coming from the tumor. If successful, this tool will be valuable in detecting liver cancer in patients as well as monitoring the response to treatment.
