Non-invasive estimation of 10 B-4-borono-L-phenylalanine-derived boron concentration in tumors by PET using 4-borono-2-18 F-fluoro-phenylalanine

Abstract

In boron neutron capture therapy (BNCT), ¹⁰ B-4-borono-L-phenylalanine (BPA) is commonly used as a ¹⁰ B carrier. PET using 4-borono-2-¹⁸ F-fluoro-phenylalanine (¹⁸ F-FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of ¹⁸ F-FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of ¹⁸ F-FBPA and BPA, and evaluated the utility of ¹⁸ F-FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid, an inhibitor of the L-type amino acid transporter, significantly inhibited ¹⁸ F-FBPA and ¹⁴ C-4-borono-L-phenylalanine (¹⁴ C-BPA) uptake in FaDu and LN-229 human cancer cells. ¹⁸ F-FBPA uptake strongly correlated with ¹⁴ C-BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of ¹⁸ F-FBPA was independent of the administration method, and uptake of ¹⁸ F-FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of ¹⁸ F-FBPA by PET was useful for estimating ¹⁰ B concentration in tumors.

Keywords: 10B-4-borono-L-phenylalanine; 4-borono-2-18F-fluoro-phenylalanine; L type amino acid transporter; PET; boron neutron capture therapy.