Validation of R-2-[ 18 F]Fluoropropionic Acid as a Potential Tracer for PET Imaging of Liver Cancer.

Purpose: 2-[ ¹⁸ F]Fluoropropionic acid (RS-[ ¹⁸ 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-[ ¹⁸ F]FPA is a mixture of 2-R-[ ¹⁸ F]fluoropropionic acid (R-[ ¹⁸ F]FPA) and 2-S-[ ¹⁸ F]fluoropropionic acid (S-[ ¹⁸ F]FPA). The aim of this study is to validate the feasibility of R-[ ¹⁸ F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[ ¹⁸ F]FPA with that of RS-[ ¹⁸ F]FPA and S-[ ¹⁸ F]FPA.
Procedures: A comparative study of R-[ ¹⁸ F]FPA, RS-[ ¹⁸ F]FPA, S-[ ¹⁸ F]FPA, and [ ¹⁸ F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[ ¹⁸ F]FPA uptake with that of S-[ ¹⁸ 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-[ ¹⁸ F]FPA were comparable to those of RS-[ ¹⁸ F]FPA but were higher than those of S-[ ¹⁸ F]FPA and 2-deoxy-2-[ ¹⁸ F]fluoro-D-glucose ([ ¹⁸ F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[ ¹⁸ F]FPA in large HepG2 tumors were lower than those of [ ¹⁸ F]FDG (P < 0.05), while R-[ ¹⁸ F]FPA PET was significantly superior to [ ¹⁸ F]FDG PET in detecting small tumors (both SK-Hep-1 and HepG2 tumors). The in vivo PET imaging experiments showed that R-[ ¹⁸ 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-[ ¹⁸ F]FPA in SK-Hep-1 tumor-bearing mice was blocked by 39.5 % with orlistat.
Conclusion: R-[ ¹⁸ F]FPA seems to be more potential than S-[ ¹⁸ F]FPA as an optically pure PET probe, with effective compensation for the deficiencies of [ ¹⁸ F]FDG, particularly in PET imaging of small liver cancer. The uptake mechanism of [ ¹⁸ F]FPA in liver cancer may be related to fatty acid synthesis and the tricarboxylic acid cycle. However, compared with the racemic RS-[ ¹⁸ F]FPA, the possible advantages of R-enantiomer R-[ ¹⁸ F]FPA still needs further research.