Reliable radiosynthesis of 4-[(10)B]borono-2-[(18)F]fluoro-l-phenylalanine with quality assurance for boron neutron capture therapy-oriented diagnosis

OBJECTIVE: The aim of this study was to establish a reliable and routine method for the preparation of 4-[(10)B]borono-2-[(18)F]fluoro-l-phenylalanine (l-[(18)F]FBPA) for boron neutron capture therapy-oriented diagnosis using positron emission tomography. METHODS: To produce l-[(18)F]FBPA by electrophilic fluorination of 4-[(10)B]borono-l-phenylalanine (l-BPA) with [(18)F]acetylhypofluorite ([(18)F]AcOF) via [(18)F]F(2) derived from the (20)Ne(d,α)(18)F nuclear reaction, several preparation parameters and characteristics of l-[(18)F]FBPA were investigated, including: pre-irradiation for [(18)F]F(2) production, the carrier F(2) content in the Ne target, l-BPA-to-F(2) ratios, separation with high-performance liquid chromatography (HPLC) using 10 different eluents, enantiomeric purity, and residual trifluoroacetic acid used as the reaction solvent by gas chromatography-mass spectrometry. RESULTS: The activity yields and molar activities of l-[(18)F]FBPA (n = 38) were 1200 ± 160 MBq and 46–113 GBq/mmol, respectively, after deuteron-irradiation for 2 h. Two 5 min pre-irradiations prior to [(18)F]F(2) production for (18)F-labeling were preferable. For l-[(18)F]FBPA synthesis, 0.15–0.2% of carrier F(2) in Ne and l-BPA-to-F(2) ratios > 2 were preferable. HPLC separations with five of the 10 eluents provided injectable l-[(18)F]FBPA without any further formulation processing, which resulted in a synthesis time of 32 min. Among the five eluents, 1 mM phosphate-buffered saline was the eluent of choice. The l-[(18)F]FBPA injection was sterile and pyrogen-free, and contained very small amounts of D-enantiomer (< 0.1% of l-[(18)F]FBPA), l-BPA (< 1% of l-FBPA), and trifluoroacetic acid (< 0.5 ppm). CONCLUSIONS: l-[(18)F]FBPA injection was reliably prepared by the electrophilic fluorination of l-BPA with [(18)F]AcOF followed by HPLC separation with 1 mM phosphate-buffered saline.