Boron neutron capture therapy with pteroyl-closo-dodecaborate-conjugated 4-(p-iodophenyl)butyric acid (PBC-IP) for a head and neck squamous cell carcinoma (SAS) model mice

Boron neutron capture therapy (BNCT) is an attractive therapeutic approach for treating refractory cancers. Currently, 4-borono-L-phenylalanine (BPA) is the only boron carrier approved for BNCT, specifically for unresectable, locally advanced, or recurrent head and neck cancers in Japan. However, efficacy of BPA relies on the L-type amino acid transporter (LAT1), which is highly expressed in many cancers, limiting its broader application. In this study, we investigated the potential of a novel boron carrier, pteroyl-closo-dodecaborate-conjugated 4-(p-iodophenyl)butyric acid (PBC-IP), designed to the folate receptors (FRs), as an alternative for BNCT in head and neck cancers. PBC-IP was injected into human head and neck squamous cell carcinoma SAS xenograft mice to assess its biodistribution and therapeutic efficacy compared to BPA. Our results showed that PBC-IP achieved selective tumor accumulation, although the boron concentration in tumors was lower than that of BPA (5 μg [¹⁰B]/g vs. 15 μg [¹⁰B]/g, respectively). PBC-IP underwent significant hepatic metabolism. BNCT treatment with PBC-IP suppressed tumor growth in mice, whereas BPA showed superior efficacy, nearly eliminating tumors. Importantly, no significant toxicity was observed in either group. These findings suggest that while PBC-IP exhibits some potential for BNCT targeting FR-expressing tumors, BPA remains the more effective option for head and neck cancer.