Pharmacokinetic, Biodistribution, and toxicity Study of Boronophenylalanine in hepatocellular carcinoma cells and Tumor- Bearing Mouse Model

Boron neutron capture therapy (BNCT) enables dual-targeted heavy-ion radiotherapy at the cellular level, with boronophenylalanine (BPA) as a key boron carrier. Although BPA shows clinical promise in liver cancer, there is relatively little basic research on its effect on hepatocellular carcinoma. Here, we systematically evaluated BPA uptake, safety, and pharmacokinetics. Boron uptake in HCC cells (Hepa1-6, HepG2) was quantified via ICP-AES, revealing concentration- and time-dependent accumulation (plateau at 6 h), while CCK-8 assays indicated significant cytotoxicity at 24 h. Hemolysis experiments confirmed BPA safety (0.1–1 mg/mL), and pharmacokinetic studies in Sprague-Dawley rats showed rapid boron distribution (peak at 25 ± 5.8 min) with a blood half-life of 74.71 ± 52.22 min. In cell-derived xenograft models, BPA achieved tumor-specific targeting, with tumor-to-normal tissue (T/N) and tumor-to-blood (T/B) ratios exceeding 2 and 4, respectively, at 2 h post-injection, followed by rapid systemic clearance. These findings demonstrate BPA selective enrichment in liver tumors, favorable pharmacokinetics, and low toxicity, supporting its clinical utility in BNCT for HCC.