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

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