[(11)C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice

Altered metabolism, including increased glycolysis and de novo lipogenesis, is one of the hallmarks of cancer. Radiolabeled nutrients, including glucose and acetate, are extensively used for the detection of various tumors, including hepatocellular carcinomas (HCCs). High signal of [(11)C]acetate positron emission tomography (PET) in tumors is often considered to be associated with increased expression of fatty acid synthase (FASN) and increased de novo lipogenesis in tumor tissues. Defining a subset of tumors with increased [(11)C]acetate PET signal and thus increased lipogenesis was suggested to help select a group of patients, who may benefit from lipogenesis-targeting therapies.

To investigate whether [(11)C]acetate PET imaging is truly associated with increased de novo lipogenesis along with hepatocarcinogenesis, we performed [(11)C]acetate PET imaging in wild-type mice as well as two mouse HCC models, induced by myrAKT/Ras(V12) (AKT/Ras) and PIK3CA(1047R)/c-Met (PI3K/Met) oncogene combinations. In addition, we analyzed FASN expression and de novo lipogenesis rate in these mouse liver tissues.

We found that while HCCs induced by AKT/Ras co-expression showed high levels of [(11)C]acetate PET signal compared to normal liver, HCCs induced by PI3K/Met overexpression did not. Intriguingly, elevated FASN expression and increased de novo lipogenesis rate were observed in both AKT/Ras and PI3K/Met HCCs.

Altogether, our study suggests that [(11)C]acetate PET imaging can be a useful tool for imaging of a subset of HCCs. However, at molecular level, the increased [(11)C]acetate PET imaging is not always associated with increased FASN expression or de novo lipogenesis.