Hepatocellular Carcinoma (HCC) is increasing in frequency and mortality in United States, and the rapid increase of HCC incidence correlates with increase in hepatitis viral infection. Early diagnosis and accurate assessment of treatment response require a reliable, localized, repeatable, and quantitative measure. Medical imaging offers such a means for non-invasive, repeated, and quantitative evaluation of the progression or status of HCC. However, the main PET tracer currently used for oncology imaging, [18F]-FDG, has been shown to be ineffective for imaging HCC since many HCCs do not show FDG uptake in contrast to the surrounding hepatic tissues, which has led to a high false negative rate. Other tracers such as [11C]- Acetate and [11C]-Choline have shown some uptake in HCC although the utilities of these existing tracers are still unclear. There is an urgent need for an effective imaging tracer that can be used in HCC for early detection and assessment of early response to treatment. In this application, we propose to study a new radiolabeled PET tracer L-FMAU for its performance in HCC imaging. The molecule was developed initially as an anti-viral agent. Its mirrored stereoisomer, D-FMAU, a nucleoside analog, has been labeled for PET imaging although its usefulness for imaging primary liver cancer such as HCC is in doubt due to the high background uptake in the liver. L-FMAU, on the other hand, is a non-natural nucleoside analog and has been the focal interest of recent radiolabeling development for PET imaging. There is a real potential for L-FMAU to be a PET tracer for imaging HCC based on our preliminary results. We will conduct thorough investigations for the mechanisms responsible for L-FMAU's transport, metabolism, degradation (or resistance to it) in the liver tissue and liver cancer, and will correlate PET imaging data with characteristics of the cancer to evaluate L-FMAU's utility i imaging HCC.

Public Health Relevance

Our study evaluates a new PET tracer for effective imaging of hepatocellular carcinoma (HCC). FDG, the available PET tracer commonly used for oncological applications, is ineffective for HCC imaging due to a high false negative rate. The new imaging tracer, L- FMAU has shown great promise. We will investigate the molecular mechanisms for its use in liver cancer imaging. Specifically, we will examine its performance for early detection and assessment of early response to the treatment of HCC. Upon successful development and evaluation as proposed, the use of this new tracer will meet the urgent need for effective PET imaging for HCC, which is increasing rapidly in frequency and mortality in United States.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Menkens, Anne E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Case Western Reserve University
Schools of Medicine
United States
Zip Code
Lee, Zhenghong; Luo, Guangbin (2014) Issues pertaining to PET imaging of liver cancer. J Fasting Health 2:62-64
Kuang, Yu; Wang, Fangjing; Corn, David J et al. (2014) Metabolism of radiolabeled methionine in hepatocellular carcinoma. Mol Imaging Biol 16:44-52
Kuang, Yu; Wang, Fangjing; Corn, David J et al. (2014) In vitro characterization of uptake mechanism of L-[methyl-(3)H]-methionine in hepatocellular carcinoma. Mol Imaging Biol 16:459-68
Tenley, Nathan; Corn, David J; Yuan, Lewis et al. (2013) The effect of fasting on PET Imaging of Hepatocellular Carcinoma. J Cancer Ther 4:561-567
Kuang, Yu; Salem, Nicolas; Tian, Haibin et al. (2011) Imaging lipid synthesis in hepatocellular carcinoma with [methyl-11c]choline: correlation with in vivo metabolic studies. J Nucl Med 52:98-106
Kolthammer, Jeffrey A; Corn, David J; Tenley, Nathan et al. (2011) PET imaging of hepatocellular carcinoma with 18F-fluoroethylcholine and 11C-choline. Eur J Nucl Med Mol Imaging 38:1248-56
Salem, Nicolas; Kuang, Yu; Corn, David et al. (2011) [(Methyl)1-(11)c]-acetate metabolism in hepatocellular carcinoma. Mol Imaging Biol 13:140-51
Lu, Xincheng; Guo, Hong; Molter, Joseph et al. (2011) Alpha-fetoprotein-thymidine kinase-luciferase knockin mice: a novel model for dual modality longitudinal imaging of tumorigenesis in liver. J Hepatol 55:96-102
Kuang, Yu; Salem, Nicolas; Corn, David J et al. (2010) Transport and metabolism of radiolabeled choline in hepatocellular carcinoma. Mol Pharm 7:2077-92
Salem, N; Kuang, Y; Wang, F et al. (2009) PET imaging of hepatocellular carcinoma with 2-deoxy-2[18F]fluoro-D-glucose, 6-deoxy-6[18F] fluoro-D-glucose, [1-11C]-acetate and [N-methyl-11C]-choline. Q J Nucl Med Mol Imaging 53:144-56

Showing the most recent 10 out of 17 publications