[(Methyl)1-11C]-Acetate Metabolism in Hepatocellular Carcinoma
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Studies have established the value of [(methyl)1-11C]-acetate ([11C]Act) combined with 2-deoxy-2[18F]fluoro-d-glucose (FDG) for detecting hepatocellular carcinoma (HCC) using positron emission tomography (PET). In this study, the metabolic fate of [11C]Act in HCC was characterized.
Experiments with acetic acid [1-14C] sodium salt ([14C]Act) were carried out on WCH-17 cells and freshly derived rat hepatocytes. PET scans with [11C]Act were also carried out on woodchucks with HCC before injection of [14C]Act. The radioactivity levels in different metabolites were quantified with thin-layer chromatography.
In WCH-17 cells, the predominant metabolite was phosphatidylcholine (PC). Regions of HCCs with the highest [11C]Act uptake had higher radioactivity accumulation in lipid-soluble compounds than surrounding hepatic tissues. In those regions, PC and triacylglycerol (TG) accumulated more radioactivity than in surrounding hepatic tissues.
High [11C]Act uptake in HCC is associated with increased de novo lipogenesis. PC and TG are the main metabolites into which the radioactive label from [11C]Act is incorporated in HCC.
Key wordsAcetate Hepatocellular carcinoma (HCC) Positron emission tomography (PET) Liver cancer Tumor metabolism Lipid Woodchuck Marmota monax
We are grateful to Dr. Ann-Marie Broome for her technical assistance in obtaining, preserving, and maintaining the cell lines used in this study. This work was supported in part by NIH/NCI CA095307 (Principal Investigator: Zhenghong Lee), a NIH Interdisciplinary Biomedical Imaging Training Program predoctoral training grant T32EB007509-02 (Principal Investigator: David L. Wilson), and a 2008 Society of Nuclear Medicine fellowship award (recipient: Nicolas Salem). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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