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

Abstract

Objective

The aim of this study was to establish a reliable and routine method for the preparation of 4-[¹⁰B]borono-2-[¹⁸F]fluoro-l-phenylalanine (l-[¹⁸F]FBPA) for boron neutron capture therapy-oriented diagnosis using positron emission tomography.

Methods

To produce l-[¹⁸F]FBPA by electrophilic fluorination of 4-[¹⁰B]borono-l-phenylalanine (l-BPA) with [¹⁸F]acetylhypofluorite ([¹⁸F]AcOF) via [¹⁸F]F₂ derived from the ²⁰Ne(d,α)¹⁸F nuclear reaction, several preparation parameters and characteristics of l-[¹⁸F]FBPA were investigated, including: pre-irradiation for [¹⁸F]F₂ production, the carrier F₂ content in the Ne target, l-BPA-to-F₂ 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-[¹⁸F]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 [¹⁸F]F₂ production for ¹⁸F-labeling were preferable. For l-[¹⁸F]FBPA synthesis, 0.15–0.2% of carrier F₂ in Ne and l-BPA-to-F₂ ratios > 2 were preferable. HPLC separations with five of the 10 eluents provided injectable l-[¹⁸F]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-[¹⁸F]FBPA injection was sterile and pyrogen-free, and contained very small amounts of D-enantiomer (< 0.1% of l-[¹⁸F]FBPA), l-BPA (< 1% of l-FBPA), and trifluoroacetic acid (< 0.5 ppm).

Conclusions

l-[¹⁸F]FBPA injection was reliably prepared by the electrophilic fluorination of l-BPA with [¹⁸F]AcOF followed by HPLC separation with 1 mM phosphate-buffered saline.