PET Imaging of Hepatocellular Carcinomas: (18)F-Fluoropropionic Acid as a Complementary Radiotracer for (18)F-Fluorodeoxyglucose

OBJECTIVE: To evaluate the preclinical value of (18)F-fluoropropionic acid ((18)F-FPA) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) for imaging HCCs. METHODS: The (18)F-FPA and (18)F-FDG uptake patterns in 3 HCC cell lines (Hep3B, HepG2, and SK-Hep1) were assessed in vitro and in vivo. The (18)F-FPA uptake mechanism was investigated using inhibition experiments with orlistat and 5-tetradecyloxy-2-furoic acid. The (18)F-FPA PET imaging was performed in different tumor animal models and compared with (18)F-FDG. We also evaluated the expressions of glucose transporter-1 (GLUT1), fatty acid synthase (FASN), and matrix metalloproteinase-2 (MMP2) in these cell lines. RESULTS: In vitro experiments showed that the radiotracer uptake patterns were complementary in the HCC cell lines. Orlistat and 5-tetradecyloxy-2-furoic acid decreased the uptake of (18)F-FPA. The tumor-to-liver ratio of (18)F-FPA was superior to that of (18)F-FDG in the SK-Hep1 and HepG2 tumors (P < .05). However, in the Hep3B tumors, the tumor-to-liver normalized uptake of (18)F-FDG was higher than (18)F-FPA (P < .01). FASN was highly expressed in cell lines with high (18)F-FPA uptake, whereas GLUT1 was highly expressed in cell lines with high (18)F-FDG uptake. The (18)F-FPA uptake correlated with FASN (r = 0.89, P = .014) and MMP2 (r = 0.77, P = .002) expressions. CONCLUSIONS: PET imaging with (18)F-FPA combined with (18)F-FDG can be an alternative for detecting HCC.