Optimization of [¹⁸F]FBPA production for clinical translation through precursor development and manufacturing route...

4-Borono-2-[¹⁸F]fluorophenylalanine ([¹⁸F]FBPA) is an important imaging agent for identifying suitable candidates for boron neutron capture therapy (BNCT). This study aimed to develop three new precursors for the no-carrier-added synthesis of [¹⁸F]FBPA and to establish corresponding automated radiosynthesis protocols suitable for routine production.

Following manual optimization, the optimized conditions were successfully translated to automated synthesis, resulting in non-decay-corrected radiochemical yields of 2.6% ± 1.3% for the BNBA-based protocol, 0.3% ± 0.1% for the P-02-based protocol, and 3.1% ± 0.0% for the P-03-based protocol, respectively. MicroPET/MR imaging and biodistribution analyses demonstrated the highest tumor uptake for [¹⁸F]FBPA-sorbitol conjugate ([¹⁸F]FBPA-Sor), followed by [¹⁸F]FBPA and [¹⁸F]FBPA-fructose conjugate ([¹⁸F]FBPA-Fr). Tumor standardized uptake values obtained from microPET/MR imaging were 1.72 ± 0.25 for [¹⁸F]FBPA, 1.29 ± 0.25 for [¹⁸F]FBPA-Fr, and 2.57 ± 0.28 for [¹⁸F]FBPA-Sor, with corresponding tumor-to-muscle (T/M) ratios of 3.34 ± 1.07, 4.64 ± 0.60, and 9.38 ± 0.88, respectively. Biodistribution studies further confirmed enhanced tumor accumulation of [¹⁸F]FBPA-Sor, with tumor uptake values of 10.46 ± 0.61, 11.51 ± 2.75, and 19.32 ± 1.57%ID/g for [¹⁸F]FBPA, [¹⁸F]FBPA-Fr, and [¹⁸F]FBPA-Sor, respectively. In addition, [¹⁸F]FBPA-Sor demonstrated the highest tumor-to-muscle and tumor-to-blood ratios, indicating that alditol conjugation significantly influences tracer pharmacokinetics and biodistribution profiles.

These findings provide practical insights into precursor design, radiosynthesis optimization, and imaging performance, offering a rational framework to guide future development and clinical translation of [¹⁸F]FBPA as a companion diagnostic for BNCT.