A Boronated Derivative of Temozolomide Showing Enhanced Efficacy in Boron Neutron Capture Therapy of Glioblastoma

• DOI: 10.3390/cells11071173
• Publication Date: 2022-04-01T01:33:03Z
• Authors: Jing Xiang; Lin Ma; Zheng Gu; Hongjun Jin; Hongbin Zhai; Jianfei Tong; Tianjiao Liang; Juan Li; Qiushi Ren; Qi Liu
• Keywords: Clonogenic assay; Temozolomide; Neutron capture; Dacarbazine

There is an incontestable need for improved treatment modality glioblastoma due to its extraordinary resistance traditional chemoradiation therapy. Boron neutron capture therapy (BNCT) may play a role in the future. We designed and synthesized 10B-boronated derivative of temozolomide, TMZB. BNCT was carried out with total radiation fluence 2.4 ± 0.3 × 1011 n/cm2. The effects TMZB were measured clonogenic cell survival assay vitro PET/CT imaging vivo. Then, phenylalanine (BPA) tested parallel comparison. IC50 cytotoxicity cells HS683 0.208 mM, which comparable temozolomide at 0.213 mM. In treatment, 0.243 mM caused 91.2% 6.4% death, while 0.239 BPA eliminated 63.7% 6.3% cells. had tumor-to-normal brain ratio 2.9 1.1 tumor-to-blood 3.8 0.2 mouse model. this model 58.2% tumor shrinkage 31 days after irradiation, number 35.2%. Therefore, by combining chemotherapy from radiotherapy heavy charged particles BNCT, TMZB-based exhibited promising potential therapeutic applications treatment.