PET imaging of hepatocellular carcinoma with anti-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in comparison with l-[S-methyl-(11)C]methionine

PURPOSE: [(11)C]methionine ([(11)C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of (11)C decay limited further clinical development of [(11)C]Met. Synthetic amino acid analog anti-1-amino-3-[(18)F]fluoro-cyclobutyl-1-carboxylic acid ([(18)F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer. This study investigated “repurposed” [(18)F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [(11)C]Met. METHODS: [(11)C]Met was synthesized in the lab, and [(18)F]FACBC was purchased from a commercial outlet. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for PET imaging. Bioinformatics analysis was performed for the expression of amino acid transporters responsible for radiotracer uptake and validated by PCR. Dynamic PET scans of [(11)C]Met and [(18)F]FACBC were acquired within 1 week. Standardized uptake value (SUV) was calculated for regions of interest (ROIs) defined over HCC and a liver background region. H&E staining and immunohistochemical (IHC) staining were performed with harvested tissues post-imaging. RESULTS: Higher expression of ACST2 and LAT1 was found in HCC than in the surrounding liver tissues. PCR validated this differential expression. [(11)C]Met and [(18)F]FACBC displayed some differences in their uptake and retention in HCC. Both peaked in HCC with an SUV of 3.5 after 10 min post-injection. Met maintained a plateaued contrast uptake in HCC to that in the liver while [(18)F]FCABC declined in HCC and liver after peak uptake. The pathological assessment revealed the liver tumor as moderately differentiated similar to the human HCC and proliferative. CONCLUSION: Both [(18)F]FACBC and [(11)C]Met showed uptake in HCC through the use of a clinically relevant animal model of woodchuck HCC. The uptake and retention of [(18)F]FACBC and [(11)C]Met depend on their metabolism and also rely on the distribution of their principal amino acid transporters.