Objective To evaluate the potential of ¹⁸F-fluoropropionic acid (¹⁸F-FPA) as a PET/CT tracer in the imaging of hepatocellular carcinoma (HCC) and to identify the mechanism underlying ¹⁸F-FPA uptake.

Methods (1) ¹⁸F-FPA was synthesized from the precursor methyl-2-bromopropionate. (2) ¹⁸F-FPA uptake by SK-Hep 1 HCC cells was quantified in vitro at different time points. To further investigate the mechanism underlying ¹⁸F-FPA uptake, the inhibitory effects of the fatty acid synthase inhibitor Orilistat and the acetyl-CoA carboxylase inhibitor 5-tetradecyloxy-2-furoic acid on ¹⁸F-FPA uptake were observed. (3) Micro-PET/CT imaging results for ¹⁸F-FPA and ¹⁸F-FDG for mouse models of human hepatocellular carcinoma SK-Hep 1 were obtained and compared. Mthe radioactivity uptake ratios of ¹⁸F-FDA and ¹⁸F-FDG were compared and analyzed with t test.

Results(1) ¹⁸F-FPA was synthesized with a yield of 45±2% through a simple process. (2) ¹⁸F-FPA uptake ratio by SK-Hep 1 cells gradually increased from (1.3±0.4)% after 5 min to (4.6 ±0.2)% after 120 min. In the cell uptake inhibition experiments, ¹⁸F-FPA uptake by SK-Hep 1 cells gradually decreased as inhibitor concentration increased. Under Orilistat and TOFA concentrations of 400 μmol, ¹⁸F-FPA uptake by SK-Hep 1 cells decreased by (40.3±4.0)% and (26.0±6.0)%, respectively. (3) ¹⁸F-FPA showed rapid and accurate tumor localization in mouse models of human hepatocellular carcinoma SK-Hep 1 with a tumor/liver ratio of 1.63±0.26. When used in ¹⁸F-FDG PET/CT imaging, the tumor/liver ratio of ¹⁸F-FPA reached 1.09±0.21. The imaging results provided by ¹⁸F-FPA were superior to those provided by ¹⁸F-FDG (t=4.055, P=0.047).

Conclusion ¹⁸F-FPA can be used as an alternative radiotracer in the detection of hepatocellular carcinoma, its uptake is related to fatty acid synthesis.