Acetate metabolism in hepatocellular carcinoma

Objectives Studies have established the usefulness of [¹¹C]acetate (ACT) combined with FDG for detecting HCC using PET, but the uptake mechanisms remain poorly understood.For the first time, Act metabolism in HCC was characterized and compared to that in normal liver.

Methods Pulse-chase experiments were performed on WCH-17 cells (adult woodchuck hepatoma-derived cell line) and on freshly-derived rat hepatocytes. The metabolites from the water- and lipid-soluble fractions were analyzed by TLC and CO₂ generation was measured. Three woodchucks were scanned with Act and injected with [¹⁴C]Act for metabolite analysis.

Results Most of the retained ¹⁴C in WCH-17 cells was found in lipids by 25 min after the pulse, with phosphatidylcholine (PC) being the predominant specie. The accumulation of ¹⁴C in rat hepatocytes was lower and most of the radiolabel was excreted as CO₂. By 25 min after the pulse, most of the retained ¹⁴C in the hepatocytes was in lipids, with PC, 1,2-diacylglycerol and/or cholesterol (DAG &/ CHO) and triacylglycerol (TG) being the main species.The results were similar in woodchucks except that [¹⁴C]TG levels were relatively higher in liver and HCC tissues. However, [¹⁴C]PC accounted for the Act accumulation difference between liver and HCC tissues.

Conclusions The radiolabel of Act is mostly excreted as CO₂ in hepatocytes while that which is retained is distributed in water- and lipid-soluble compounds. Act is mostly incorporated into PC in HCC. These different metabolic fates are responsible for the contrast between HCCs and surrounding liver tissues seen on Act PET images.