Quantitative PET Imaging of Hepatocellular Carcinoma (HCC)

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PROJECT SUMMARY/ABSTRACT: Quantitative PET Imaging of Hepatocellular Carcinoma Clinical decisions regarding the treatment of patients with hepatocellular carcinoma (HCC) remain largely guided by conventional, anatomical imaging modalities. These methods, namely magnetic resonance imaging (MRI) and x-ray computed tomography (CT), provide little information about the cellular and molecular underpinnings of individual tumors. HCC is the most common primary tumor of the liver and represents a major healthcare challenge in the United States (US) and elsewhere. The American Cancer Society estimates diagnosis of greater than 42,000 new cases of liver cancer in the US this year. In contrast to cancers more frequently diagnosed in the US and for which precision cancer medicine is routinely employed, such as colon or breast, incidence of liver cancer and liver cancer-associated deaths are both increasing. Improved tools to detect HCC at early, potentially curable stages, and tools to predict future tumor behavior are urgently needed. Molecular imaging with positron emission tomography (PET) is uniquely poised to provide those tools, yet novel tracers are required. The sensitivity of routine 18F-FDG PET, the most commonly utilized approach in clinical oncology, is limited in HCC, and other tracers that exhibit greater potential, such as 11C-acetate, suffer technical limitations that prevent their broad clinical use. The overarching goal of this application is to clinically evaluate an innovative PET imaging tracer that has the potential to personalize decision making in the care of patients with HCC. We propose to conduct the first quantitative imaging clinical trial of (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid (18F-FSPG) PET in the setting of HCC. As an emerging PET tracer reflecting tumor glutamate transport, 18F-FSPG PET has shown clinical safety and efficacy in multiple tumor settings, including breast, lung, and brain cancer. Our preliminary data in a pilot cohort of Vanderbilt patients, as well as a pilot clinical study conducted in Asia (n = 5), suggest the feasibility of using 18F-FSPG PET to improve the detection of HCCs even among cirrhosis, a comorbidity that diminishes the effectiveness of conventional imaging approaches. Our study has three Specific Aims. In patients undergoing surgery for treatment of HCC, we will (1) evaluate the relationship between 18F-FSPG PET, pathology and cancer metabolism; (2) compare 18F-FSPG PET with standard-of-care (SOC) diagnostic imaging in patients with HCC and benign liver lesions; and (3) compare uptake of 18F-FSPG with 11C-acetate and 18F-FDG in HCC and background liver. This study has the potential to establish a new role for non-invasive molecular imaging in the delivery of individualized cancer care for patients with HCC.