期刊
CELLS
卷 9, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cells9051277
关键词
boron-containing alpha-d-mannopyranoside; closo-dodecarborate; low-molecular-weight compound; BNCT
类别
资金
- Ajinomoto Co., Inc. [CGE 26222K, 18H02909]
- Japanese Ministry of Education, Culture, Sports, Science and Technology
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 B-10 delivery agents. However, continuous drug administration at high concentrations is needed to maintain sufficient B-10 concentration within tumors. To address the issue of B-10 accumulation and retention in tumor tissue, we developed MMT1242, a novel boron-containing alpha -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 B-10-MMT1242 is a candidate for further clinical BNCT studies.
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