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Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT

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 (10)B delivery agents. However, continuous drug administration at high concentrations i...

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Detalles Bibliográficos
Autores principales: Tsurubuchi, Takao, Shirakawa, Makoto, Kurosawa, Wataru, Matsumoto, Kayo, Ubagai, Risa, Umishio, Hiroshi, Suga, Yasuyo, Yamazaki, Junko, Arakawa, Akihiro, Maruyama, Yutaka, Seki, Takuya, Shibui, Yusuke, Yoshida, Fumiyo, Zaboronok, Alexander, Suzuki, Minoru, Sakurai, Yoshinori, Tanaka, Hiroki, Nakai, Kei, Ishikawa, Eiichi, Matsumura, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290312/
https://www.ncbi.nlm.nih.gov/pubmed/32455737
http://dx.doi.org/10.3390/cells9051277
Descripción
Sumario: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 (10)B delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient (10)B concentration within tumors. To address the issue of (10)B 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 (10)B-MMT1242 is a candidate for further clinical BNCT studies.