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

Koji Takeuchi,Shin-Ichi Miyatake,Masahiko Wanibuchi,Ryo Hiramatsu,Hiroki Tanaka,Shin-Ichiro Masunaga,Shinji Kawabata,Mitsunori Kirihata,Gen Futamura,Yoshihide Hattori,Koji Ono

doi:10.3390/cells9061551

Abstract

Boron neutron capture therapy (BNCT) is a form of tumor-cell selective particle irradiation using low-energy neutron irradiation of boron-10 (10B) to produce high-linear energy transfer (LET) alpha particles and recoiling 7Li nuclei (10B [n, alpha] 7Li) in tumor cells. Therefore, it is important to achieve the selective delivery of large amounts of 10B to tumor cells, with only small amounts of 10B to normal tissues. To develop practical materials utilizing 10B carriers, we designed and synthesized novel dodecaboranethiol (BSH)-containing kojic acid (KA-BSH). In the present study, we evaluated the effects of this novel 10B carrier on cytotoxicity, 10B 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.

Highlights

Malignant gliomas are the most common malignant primary brain tumors in adults [1].These tumors are resistant to conventional therapy, including surgery, chemotherapy, and radiation therapy
KA-BSH2NMe was treated with amberlite IR-120(H+ ) and KA-BSH tetramethylammonium salt [18]
KA-BSH2NMe44 was treated with amberlite IR-120(H+) and subsequently neutralized with

Summary

Introduction

Malignant gliomas are the most common malignant primary brain tumors in adults [1].These tumors are resistant to conventional therapy, including surgery, chemotherapy, and radiation therapy. Malignant gliomas are the most common malignant primary brain tumors in adults [1]. BNCT is based on the nuclear capture and fission reactions that occur when nonradioactive boron-10 (10 B) is irradiated with neutrons of the appropriate energy to yield high linear energy transfer (LET) alpha particles (4 He) and recoiling lithium-7 (7 Li) nuclei. Because these particles have path lengths of approximately 5–9 μm, which is one cell diameter, the destructive effect is limited to

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Conclusion