Open AccessArticle
Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT
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Takao Tsurubuchi, Makoto Shirakawa, Wataru Kurosawa, Kayo Matsumoto, Risa Ubagai, Hiroshi Umishio, Yasuyo Suga, Junko Yamazaki, Akihiro Arakawa, Yutaka Maruyama, Takuya Seki, Yusuke Shibui, Fumiyo Yoshida, Alexander Zaboronok, Minoru Suzuki, Yoshinori Sakurai, Hiroki Tanaka, Kei Nakai, Eiichi Ishikawa and Akira Matsumura
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Abstract
Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as
10B delivery agents. However, continuous drug administration at high concentrations is needed
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Boron neutron capture therapy (BNCT) is a unique anticancer technology that has demonstrated its efficacy in numerous phase I/II clinical trials with boronophenylalanine (BPA) and sodium borocaptate (BSH) used as
10B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient
10B concentration within tumors. To address the issue of
10B accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing α-
d-mannopyranoside. We evaluated the uptake, intracellular distribution, and retention of MMT1242 in cultured cells and analyzed biodistribution, tumor-to-normal tissue ratio and toxicity in vivo. Fluorescence imaging using nitrobenzoxadiazole (NBD)-labeled MMT1242 and inductively coupled mass spectrometry (ICP-MS) were performed. The effectiveness of BNCT using MMT1242 was assessed in animal irradiation studies at the Kyoto University Research Reactor. MMT1242 showed a high uptake and broad intracellular distribution in vitro, longer tumor retention compared to BSH and BPA, and adequate tumor-to-normal tissue accumulation ratio and low toxicity in vivo. A neutron irradiation study with MMT1242 in a subcutaneous murine tumor model revealed a significant tumor inhibiting effect if injected 24 h before irradiation. We therefore report that
10B-MMT1242 is a candidate for further clinical BNCT studies.
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