Boron Accumulation in Brain Tumor Cells through Boc-Protected Tryptophan as a Carrier for Boron Neutron Capture Therapy

Chun-Ming Chio; Ying-Cheng Huang; You-Cheng Chou; Fu-Chun Hsu; Yen-Buo Lai; Chung-Shan Yu

doi:10.1021/acsmedchemlett.0c00064

Boron Accumulation in Brain Tumor Cells through Boc-Protected Tryptophan as a Carrier for Boron Neutron Capture Therapy

ACS Med Chem Lett. 2020 Mar 16;11(4):589-596. doi: 10.1021/acsmedchemlett.0c00064. eCollection 2020 Apr 9.

Authors

Chun-Ming Chio¹, Ying-Cheng Huang², You-Cheng Chou¹, Fu-Chun Hsu¹, Yen-Buo Lai¹, Chung-Shan Yu^{1

3}

Affiliations

¹ Department of Biomedical Engineering and Environmental Sciences, National Tsinghua University, Hsinchu 300, Taiwan.
² Department of Neurosurgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan City 33302, Taiwan.
³ Institute of Nuclear Engineering and Science, National Tsinghua University, Hsinchu 300, Taiwan.

Abstract

Boron neutron capture therapy (BNCT) is a binary therapeutic approach. Nonradioactive boron-10 atoms accumulated in tumor cells combining with the neutron beams produce two highly energetic particles that could eradicate the cell that takes it and the neighboring cells. Small molecules that carry boron atom, e.g. 5- and 6-boronated and 2,7-diboronated tryptophans, were assessed for their boron accumulation in U87-MG, LN229, and 3T3 for BNCT. TriBoc tryptophan, TB-6-BT, shows boron-10 at 300 ppm in both types of tumor cells with a tumor to normal ratio (T/N) of 5.19-5.25 (4 h). TB-5-BT and DBA-5-BT show boron-10 at 300 ppm (2 h) in U87-MG cells. TB-5-BT exerts a T/N of >9.66 (1 h) in LN229 compared with the current clinical boronophenyl alanine with a highest T/N of 2.3 (1 h) and accumulation concentration of <50 ppm. TB-5-BT and TB-6-BT warrant further animal study.