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2-[18F]Fluoropropionic acid (RS-[18F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[18F]FPA is a mixture of 2-R-[18F]fluoropropionic acid (R-[18F]FPA) and 2-S-[18F]fluoropropionic acid (S-[18F]FPA). The aim of this study is to validate the feasibility of R-[18F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[18F]FPA with that of RS-[18F]FPA and S-[18F]FPA. A comparative study of R-[18F]FPA, RS-[18F]FPA, S-[18F]FPA, and [18F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[18F]FPA uptake with that of S-[18F]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. The radioactivity uptake values of R-[18F]FPA were comparable to those of RS-[18F]FPA but were higher than those of S-[18F]FPA and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[18F]FPA in large HepG2 tumors were lower than those of [18F]FDG (P

2-18F-Fluoropropionic acid (18F-FPA), a fluorinated analog of 11C-acetate, shows great potential for positron emission tomography (PET) imaging of prostate cancer. The present study reports a simple automated synthesis using cartridges purification, which affords 18F-FPA suitable for human use. Automated synthesis of 18F-FPA was performed using two-step one-pot synthesis procedure, consisting of [18F]fluorination of methyl-2-bromopropionate, hydrolysis with sodium hydroxide, and purification with a series of commercial solid-phase extraction cartridges instead of a high-performance liquid chromatography system. Automated synthesis of 18F-FPA was also carried out via the on-column hydrolysis on the HLB cartridges, using a similar procedure to the automated synthesis of 18F-fluoro-2-deoxy- d-glucose (18F-FDG). Using one-pot procedures on the commercial modified PET-MF-2V-IT-I synthesizer, the final 18F-FPA solution could be obtained with high uncorrected radiochemical yields (>35%) and radiochemical purity (>95%). For the on-column hydrolysis procedure, the uncorrected radiochemical yield of 18F-FPA was 46 ± 7% (n = 5, based on [18F]fluoride) within 36 min and the radiochemical purity was above 95% with the specific activity of 40 GBq/µmol. Automated synthesis of 18F-FPA by on-column hydrolysis procedure is similar to the 18F-FDG synthesis, and it can easily be applied to the automated synthesis of 18F-FPA on the commercial 18F-FDG synthesizer. Copyright © 2012 John Wiley & Sons, Ltd.

There is a high interest in developing an (18)F-labeled PET tracer that can aid in diagnosis and therapy monitoring of prostate cancer. In the current study, we have evaluated the potential of 2-(18)F-fluoropropionic acid ((18)F-FPA) as a PET tracer for imaging prostate cancer.(18)F-FPA was synthesized starting from methyl-2-bromopropionate. Small-animal PET studies were performed on mice with CWR22rv1, PC-3, DU-145, and LNCaP prostate xenografts, and comparison of imaging characteristics of (18)F-FPA with (18)F-FDG uptake is reported. Biodistribution studies with (18)F-FPA were performed on mice with CWR22rv1 xenografts and compared with (14)C-acetate.(18)F-FPA was synthesized in 44% overall radiochemical yield (decay-corrected). Small-animal PET studies revealed that (18)F-FPA can delineate both androgen-dependent and androgen-independent prostate xenografts with high tumor-to-background ratios. Comparative imaging studies demonstrate the superior performance of (18)F-FPA over (18)F-FDG for imaging prostate cancer, with excellent tumor-to-background contrast. Biodistribution studies show that tumor uptake of the tracer was 5.52 +/- 0.35, 5.53 +/- 0.42, 5.74 +/- 0.54, and 5.34 +/- 0.19 percentage injected dose (%ID) per gram at 1, 2, 3, and 4 h, respectively, after injection. The %ID/g values for (18)F-FPA and (14)C-acetate 1 h after tail vein injection were 7.08 +/- 0.80 and 0.36 +/- 0.08 in tumor, and the corresponding tumor-to-muscle ratios were 1.94 and 2.06, respectively.The data presented here indicate that (18)F-FPA accumulates in prostate cancers with high tumor-to-background ratios. (18)F-FPA has potential for use in the clinical diagnosis of prostate cancer in humans.

The aim of this study was to compare the properties and feasibility of the glucose analog, 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), three short (18)F-labeled carboxylic acids, (18)F-fluoroacetate ((18)F-FAC), 2-(18)F-fluoropropionic acid ((18)F-FPA) and 4-((18)F)fluorobenzoic acid ((18)F-FBA), for differentiating tumors from inflammation.Biodistributions of (18)F-FAC, (18)F-FPA and (18)F-FBA were determined on normal Kunming mice, and positron emission tomography (PET) imaging with these tracers were performed on the separate tumor-bearing mice model and inflammation mice model in comparison with (18)F-FDG.Biodistribution results showed that (18)F-FAC and (18)F-FPA had similar biodistribution profiles and the slow radioactivity clearance from most tissues excluding the in vivo defluorination of (18)F-FAC, and (18)F-FBA demonstrated a lower uptake and fast clearance in most tissues. PET imaging with (18)F-FDG, (18)F-FAC and (18)F-FPA revealed the high uptake in both tumor and inflammatory lesions. The ratios of tumor-to-inflammation were 1.63 ± 0.28 for (18)F-FDG, 1.20 ± 0.38 for (18)F-FAC, and 1.41 ± 0.33 for (18)F-FPA at 60 min postinjection, respectively. While clear tumor images with high contrast between tumor and inflammation lesion were observed in (18)F-FBA/PET with the highest ratio of tumor-to-inflammation (1.98 ± 0.15).Our data demonstrated (18)F-FBA is a promising PET probe to distinguish tumor from inflammation. But the further modification of (18)F-FBA structure is required to improve its pharmacokinetics.