Yang Ji-Ung, Kim Soyeon, Lee Kyo Chul, Lee Yong Jin, Kim Jung Young, Park Ji-Ae
Division of Applied RI, Korea Institute of Radiological & Medical Sciences (KIRAMS), Seoul 01812, Korea.
Department of Medical & Biological Engineering, Kyungpook National University, Daegu 41566, Korea.
ACS Med Chem Lett. 2022 Sep 15;13(10):1615-1620. doi: 10.1021/acsmedchemlett.2c00284. eCollection 2022 Oct 13.
Boron neutron capture therapy (BNCT) is a precision treatment technology that ideally damages only boron-accumulating cells. The effectiveness of BNCT depends on the amount of boron in the tumor cells and the concentration ratio between normal and tumor tissues. Therefore, for successful brain-tumor treatment using BNCT, it is essential to develop a drug with high blood-brain barrier (BBB) permeability and high tumor accumulation. The benzothiazole-based boron complex 4-(benzo[]thiazol-2-yl)phenylboronic acid (BTPB) is a hydrophobic, low-molecular-weight compound that has shown high BBB permeability and brain accumulation. The highest boron concentration of BTPB is 36.11 ± 2.73 μg/g (at 1 h post-injection) in the brain, and the highest brain/blood ratio is 3.94 ± 0.46 (at 2 h post-injection), which is sufficient for the BNCT drug condition. In addition, BTPB showed good tumor-targeting ability in a U87MG glioma tumor model. In this study, we conducted a biological evaluation of BTPB compared to boronophenylalanine as a novel drug for BNCT.
硼中子俘获疗法（BNCT）是一种精准治疗技术，理想情况下仅对积累硼的细胞造成损伤。BNCT的有效性取决于肿瘤细胞中硼的含量以及正常组织与肿瘤组织之间的浓度比。因此，要使用BNCT成功治疗脑肿瘤，开发一种具有高血脑屏障（BBB）通透性和高肿瘤蓄积性的药物至关重要。基于苯并噻唑的硼配合物4-（苯并[][1,3]噻唑-2-基）苯硼酸（BTPB）是一种疏水性低分子量化合物，已显示出高BBB通透性和脑蓄积性。BTPB在脑中的最高硼浓度为36.11±2.73μg/g（注射后1小时），最高脑/血比为3.94±0.46（注射后2小时），这足以满足BNCT药物条件。此外，BTPB在U87MG胶质瘤肿瘤模型中显示出良好的肿瘤靶向能力。在本研究中，我们对BTPB与硼苯丙氨酸作为BNCT新药进行了生物学评价。
