The use of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) as a predictor of metastasis and response to inhibition of glucose metabolism.

Objectives The aim of this study was to investigate whether 18F-FDG PET/CT is useful imaging modality to predict metastasis in patient with hepatocellular carcinoma (HCC) and response to inhibition of glucose metabolism of HCC tumor cells.

Methods We retrospectively enrolled total one hundred-sixteen patient with early HCC treated curative surgical resection who underwent 18F-FDG PET/CT for preoperative staging. During follow up, all patients were grouped according to whether they had distant metastasis. We investigated the correlation between 18F-FDG PET parameter and metastasis pattern. Among these patients, we selected thirteen patients with low FDG uptake (TLR≤1.62) and seven patients with high FDG uptake (TLR>1.62) and analyzed expression of the epithelial-mesenchymal transition (EMT) markers by immunohistochemistry. To assess the relationship between FDG uptake and response to inhibition of glucose metabolism, we employed well-characterized HCC cell lines having different 18F-FDG uptake (SNU475 and Hep3B). In vitro assays assessing proliferation (MTT) and migration (Boyden chamber) were then performed.

Results During the median follow up of 34.5 months of 116 patients with HCC, 10 patients (29.4%) had distant metastasis in patient with the high tumor to liver SUV ratio (n=34) and 6 patients (7.3%) had distant metastasis in patient with the low tumor to liver SUV ratio (n=82). There was statistically significant difference in frequency of distant metastasis according to tumor to liver SUV ratio (P=0.002). Interestingly, we also observed that HCC with high FDG uptake showed higher expression of EMT markers compare to HCC with low FDG uptake. Additionally, we found that reduction of cell proliferation and migration after treatment with inhibitor of glucose metabolism in HCC cell lines were correlated to FDG uptake in vitro.

Conclusions Altogether, our data demonstrate that 18F-FDG PET has an important role in the prediction of metastasis in patients with HCC. Moreover, 18F-FDG uptake may represent a surrogate marker of therapy response to inhibitor of glucose metabolism.