Predominant contribution of L-type amino acid transporter to 4-borono-2-18F-fluoro-phenylalanine uptake in human glioblastoma cells

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-C-11]-methionine (C-11-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 C-14-MET in human glioblastoma cell lines. Methods: Uptake of (18) F-FBPA and C-14-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 C-14-MET (48.3%-59.4%). System A and ASC also contributed to the uptake of C-14-MET. Inhibition experiments revealed that BPA significantly decreased the uptake of (18) F-FBPA, whereas 31%-42% of total C-14-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 C-14-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. (C) 2013 Elsevier Inc. All rights reserved.