Validation of R-2-[F]Fluoropropionic Acid as a Potential Tracer for PET Imaging of Liver Cancer.

Purpose: 2-[F]Fluoropropionic acid (RS-[F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[F]FPA is a mixture of 2-R-[F]fluoropropionic acid (R-[F]FPA) and 2-S-[F]fluoropropionic acid (S-[F]FPA). The aim of this study is to validate the feasibility of R-[F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[F]FPA with that of RS-[F]FPA and S-[F]FPA.

Procedures: A comparative study of R-[F]FPA, RS-[F]FPA, S-[F]FPA, and [F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[F]FPA uptake with that of S-[F]FPA by HepG2 and SK-Hep-1 cells was made at different time points. Additionally, in vivo blocking experiments in HepG2 and SK-Hep-1 tumor models were conducted with orlistat and 3-nitropropionic acid (3-NP). In vitro blocking experiments with orlistat or 3-NP were performed with HepG2 and SK-Hep-1 cells.

Results: The radioactivity uptake values of R-[F]FPA were comparable to those of RS-[F]FPA but were higher than those of S-[F]FPA and 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[F]FPA in large HepG2 tumors were lower than those of [F]FDG (P < 0.05), while R-[F]FPA PET was significantly superior to [F]FDG PET in detecting small tumors (both SK-Hep-1 and HepG2 tumors). The in vivo PET imaging experiments showed that R-[F]FPA uptake in HepG2 tumor-bearing mice was blocked by 19.3 % and 31.8 % after treatment with orlistat and 3-NP, respectively. The radioactivity uptake values of R-[F]FPA in SK-Hep-1 tumor-bearing mice was blocked by 39.5 % with orlistat.

Conclusion: R-[F]FPA seems to be more potential than S-[F]FPA as an optically pure PET probe, with effective compensation for the deficiencies of [F]FDG, particularly in PET imaging of small liver cancer. The uptake mechanism of [F]FPA in liver cancer may be related to fatty acid synthesis and the tricarboxylic acid cycle. However, compared with the racemic RS-[F]FPA, the possible advantages of R-enantiomer R-[F]FPA still needs further research.