Aim: This study was designed to investigate the performance of positron emission tomography (PET) imaging for hepatocellular carcinoma (HCC) on a hepatitis viral infection-induced woodchuck model using existing tracers such as 2-deoxy-2[(18)F]fluoro-D-glucose (2FDG), 6-deoxy-6[(18)F]fluoro-D-glucose (6FDG), [1(-11)C]acetate (acetate) and [N-methyl(-11)C]choline (choline).
Methods: Fourteen woodchucks with HCC were imaged with different radiotracers: 13 (10 with HCC and 3 controls) with 2FDG; 4 (3 with HCC and 1 control) with 6FDG; 13 (10 with HCC and 3 controls) with acetate; 4 (2 with HCC and 2 controls) with choline. The woodchucks were euthanized after imaging experiments and liver tissues were harvested for histology, for enzymatic activities including hexokinase (HK), glucose-6-phosphatase, acetyl-CoA synthetase (ACAS) and choline kinase (CK), and for differential gene expressions between the HCCs and the surrounding hepatic tissues.
Results: 2FDG detected 7/13 tumors with a tumor-to-liver uptake ratio (T/L) of 1.36+/-0.13. Five of these HCCs were moderately- or poorly-differentiated. The HK/glucose-6-phosphatase ratio was significantly higher in HCCs compared to the surrounding liver tissues (P=0.05). None of the HCCs imaged with 6FDG were detected by PET (T/L=1.01+/-0.11). Acetate detected 16/17 HCCs (T/L=2.02+/-0.7). ACAS activity was significantly higher in HCCs (P=0.01) and lipids-related genes were found up-regulated. Choline imaging detected all HCCs (T/L=1.63+/-0.34). CK activity was significantly higher in HCCs (P=0.001).
Conclusions: Well-differentiated and some moderately-differentiated HCCs do not uptake 2FDG more than the surrounding liver tissues, but display increased acetate uptake. There is no contrast between HCCs and the surrounding liver tissues on the 6FDG PET images. Despite elevated background signal from the liver, choline uptake seems to be detectable in the HCCs scanned in this study.