TY - JOUR T1 - The Importance of Acetyl Coenzyme A Synthetase for <sup>11</sup>C-Acetate Uptake and Cell Survival in Hepatocellular Carcinoma JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1222 LP - 1228 DO - 10.2967/jnumed.109.062703 VL - 50 IS - 8 AU - Mijin Yun AU - Seong-Hye Bang AU - Jae Woo Kim AU - Jun Young Park AU - Kyoung Sup Kim AU - Jong Doo Lee Y1 - 2009/08/01 UR - http://jnm.snmjournals.org/content/50/8/1222.abstract N2 - We analyzed the pattern of 11C-acetate and 18F-FDG uptake on PET/CT in patients with hepatocellular carcinoma (HCC). We also assessed the expression of important regulatory enzymes related to glycolysis and lipid synthesis in relation to 18F-FDG and 11C-acetate uptake in human HCC cell lines. The significance of 11C-acetate uptake regulation was further evaluated with regard to cell viability. Methods: 18F-FDG and 11C-acetate uptake patterns in HCC in 11 patients and in 5 HCC cell lines were assessed. We evaluated the gene expression of metabolic enzymes related to glycolysis and lipid synthesis in a cell line with the highest 18F-FDG uptake and another cell line with the highest 11C-acetate uptake. They included hexokinase II, adenosine triphosphate citrate lyase, acetyl coenzyme A (CoA) synthetase 1 (ACSS1), acetyl CoA synthetase 2 (ACSS2), acetyl CoA carboxylase, and fatty acid synthase. In a cell line with high 11C-acetate uptake, the enzymatic activities of ACSS1 and ACSS2 were blocked using respective small, interfering RNAs (siRNAs), and the impact on 11C-acetate uptake and cell viability was assessed. Results: In all 11 patients and 4 of the 5 cell lines, the uptake patterns of the 2 radiotracers were complementary. ACSS1 and ACSS2 were highly expressed in a cell line with low 18F-FDG uptake and high 11C-acetate uptake, whereas only ACSS2 was expressed in a cell line with high 18F-FDG uptake and low 11C-acetate uptake. Fatty acid synthase expression was seen in cells with high 18F-FDG or 11C-acetate uptake. These findings indicate the possibility that both glucose and acetate can be a compensatory carbon source for lipid synthesis in cancer. Transient transfection with ACSS1 or ACSS2 siRNA in cells with high 11C-acetate uptake decreased 11C-acetate uptake and cell viability. Conclusion: The patterns of 18F-FDG and 11C-acetate uptake seemed to complement each other in both human HCC and HCC cell lines. Fatty acid synthase expression was seen in cells with high 18F-FDG or 11C-acetate uptake, suggesting glucose- or acetate-dependent lipid synthesis. Acetyl CoA synthetase appears to be important in 11C-acetate uptake and acetate-dependent lipid synthesis for the growth of cancer cells with a low-glycolysis phenotype. Inhibition of acetyl CoA synthetase in these cells may be promising for anticancer treatment. ER -