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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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 |
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author | 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 |
author_facet | 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 |
author_sort | Tsurubuchi, Takao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7290312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72903122020-06-15 Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT 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 Cells Article 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. MDPI 2020-05-21 /pmc/articles/PMC7290312/ /pubmed/32455737 http://dx.doi.org/10.3390/cells9051277 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT |
title | Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT |
title_full | Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT |
title_fullStr | Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT |
title_full_unstemmed | Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT |
title_short | Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT |
title_sort | evaluation of a novel boron-containing α-d-mannopyranoside for bnct |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290312/ https://www.ncbi.nlm.nih.gov/pubmed/32455737 http://dx.doi.org/10.3390/cells9051277 |
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