Imaging of lipid synthesis in hepatocellular carcinoma correlated with metabolism study in vivo

Objectives PET imaging of lipid synthesis with choline (CHOL) can be useful in well-differentiated hepatocellular carcinoma (HCC) that is not FDG avid.In this study, the woodchuck model of HCC was imaged by ¹¹C-CHOL and correlated with the ¹⁴C-CHOL metabolism in vivo, which helped to elucidate the role and impact of CHOL in interpreting the PET imaging data.

Methods Dynamic PET scans of ¹¹C-CHOL were acquired on woodchuck model. After imaging, ¹⁴C-CHOL was injected and metabolites from HCC and surrounding hepatic tissue (SHT) were extracted and analyzed by HPLC. CHOL kinase (ChoK) and CHOL-phosphate cytidyldyltransferase (CCT) activities were also correlated with the imaging and metabolism data.

Results CHOL tracer showed higher uptake in HCC than in SHT. The big variance of radioactivity distribution within HCCs indicated a heterogeneous uptake of CHOL, which is related with the growth pattern and grade of HCC. HCC has a higher ChoK and CCT activities than SHT. The major metabolites were phosphocholine (PCho) in HCC and betaine and CHOL in SHT at 12 min. PCho rapidly converted to phosphatidylcholine (PC) in HCC at 30 min, whose accumulation pattern is different with those in vitro data and the data using xenograft model.

Conclusions Our data suggest that the imaging contrast in HCC attributed to the PC synthesis. The discrepancy between in vitro and in vivo can potentially be attributed to the distinct microenvironment between HCC and SHT with changed fatty acid profiles in HCC causing the activation of CCT activity in HCC. Future studies with woodchucks on different CHOL metabolism will allow us to image both well- and poorly- differentiated HCCs.

Research Support NIH R01 CA095307