Development of Brain-Tumor-Targeted Benzothiazole-Based Boron Complex for Boron Neutron Capture Therapy

Ji-Ung Yang; Soyeon Kim; Kyo Chul Lee; Yong Jin Lee; Jung Young Kim; Ji-Ae Park

doi:10.1021/acsmedchemlett.2c00284

Development of Brain-Tumor-Targeted Benzothiazole-Based Boron Complex for Boron Neutron Capture Therapy

ACS Med Chem Lett. 2022 Sep 15;13(10):1615-1620. doi: 10.1021/acsmedchemlett.2c00284. eCollection 2022 Oct 13.

Authors

Ji-Ung Yang^{1

2}, Soyeon Kim^{1

2}, Kyo Chul Lee¹, Yong Jin Lee¹, Jung Young Kim¹, Ji-Ae Park¹

Affiliations

¹ Division of Applied RI, Korea Institute of Radiological & Medical Sciences (KIRAMS), Seoul 01812, Korea.
² Department of Medical & Biological Engineering, Kyungpook National University, Daegu 41566, Korea.

Abstract

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[d]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 vivo 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.