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Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 ( 10 B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7 Li nuclei ( 10 B [n, alpha] 7 Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of 10 B to tumor cells, with only small amounts of 10 B to normal tissues. To develop practical materials utilizing 10 B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH). In the present study, we evaluated the effects of this novel 10 B carrier on cytotoxicity, 10 B concentrations in F98 rat glioma cells, and micro-distribution of KA-BSH in vitro. Furthermore, biodistribution studies were performed in a rat brain tumor model. The tumor boron concentrations showed the highest concentrations at 1 h after the termination of administration. Based on these results, neutron irradiation was evaluated at the Kyoto University Research Reactor Institute (KURRI) with KA-BSH. Median survival times (MSTs) of untreated and irradiated control rats were 29.5 and 30.5 days, respectively, while animals that received KA-BSH, followed by neutron irradiation, had an MST of 36.0 days ( p = 0.0027, 0.0053). Based on these findings, further studies are warranted in using KA-BSH as a new B compound for malignant glioma.

Synthesis and Evaluation of Dodecaboranethiol Containing Kojic Acid (KA-BSH) as a Novel Agent for Boron Neutron Capture Therapy