INTRODUCTION: 4-Borono-2-(18)F-fluoro-phenylalanine ((18)F-FBPA) has been used to anticipate the therapeutic effects of boron neutron capture therapy (BNCT) with 4-borono-L-phenylalanine (BPA). Similarly, L-[methyl-(11)C]-methionine ((11)C-MET), the most popular amino acid PET tracer, is a possible candidate for this purpose. We investigated the transport mechanism of (18)F-FBPA and compared it with that of (14)C-MET in human glioblastoma cell lines. METHODS: Uptake of (18)F-FBPA and (14)C-MET was examined in A172, T98G, and U-87MG cells using 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (a system L-specific substrate), 2-(methylamino)-isobutyric acid (a system A-specific substrate), and BPA. Gene expression was analyzed by quantitative real time polymerase chain reaction. RESULTS: System L was mainly involved in the uptake of (18)F-FBPA (74.5%-81.1% of total uptake) and (14)C-MET (48.3%-59.4%). System A and ASC also contributed to the uptake of (14)C-MET. Inhibition experiments revealed that BPA significantly decreased the uptake of (18)F-FBPA, whereas 31%-42% of total (14)C-MET uptake was transported by BPA non-sensitive transporters. In addition, (18)F-FBPA uptake correlated with LAT1 and total LAT expressions. CONCLUSION: This study demonstrated that (18)F-FBPA was predominantly transported by system L in human glioblastoma cells compared to (14)C-MET. Although further studies are needed to elucidate the correlation between (18)F-FBPA uptake and BPA content in tumor tissues, (18)F-FBPA is suitable for the selection of patients who benefit from BNCT with BPA.
INTRODUCTION:4-Borono-2-(18)F-fluoro-phenylalanine ((18)F-FBPA) has been used to anticipate the therapeutic effects of boron neutron capture therapy (BNCT) with 4-borono-L-phenylalanine (BPA). Similarly, L-[methyl-(11)C]-methionine ((11)C-MET), the most popular amino acid PET tracer, is a possible candidate for this purpose. We investigated the transport mechanism of (18)F-FBPA and compared it with that of (14)C-MET in humanglioblastoma cell lines. METHODS: Uptake of (18)F-FBPA and (14)C-MET was examined in A172, T98G, and U-87MG cells using 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (a system L-specific substrate), 2-(methylamino)-isobutyric acid (a system A-specific substrate), and BPA. Gene expression was analyzed by quantitative real time polymerase chain reaction. RESULTS: System L was mainly involved in the uptake of (18)F-FBPA (74.5%-81.1% of total uptake) and (14)C-MET (48.3%-59.4%). System A and ASC also contributed to the uptake of (14)C-MET. Inhibition experiments revealed that BPA significantly decreased the uptake of (18)F-FBPA, whereas 31%-42% of total (14)C-MET uptake was transported by BPA non-sensitive transporters. In addition, (18)F-FBPA uptake correlated with LAT1 and total LAT expressions. CONCLUSION: This study demonstrated that (18)F-FBPA was predominantly transported by system L in humanglioblastoma cells compared to (14)C-MET. Although further studies are needed to elucidate the correlation between (18)F-FBPA uptake and BPA content in tumor tissues, (18)F-FBPA is suitable for the selection of patients who benefit from BNCT with BPA.