Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China.
Department of Radiology, The Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, PR China.
Appl Radiat Isot. 2024 Jul;209:111330. doi: 10.1016/j.apradiso.2024.111330. Epub 2024 Apr 23.
Boron neutron capture therapy (BNCT) has received extensive attention as an advanced binary radiotherapy method. However, BNCT still faces poor selectivity of boron agent and is insufficient boron content in tumor tissues. To improve the tumor-targeted ability and boron content, this research aims to design, synthesize and preliminary evaluate a new borane agent Carborane-FAPI, which coupling the o-carborane to the compound skeleton of a mature fibroblast activating protein (FAP) inhibitor (FAPI). FAP is a tumor-associated antigen. FAP expressed lowly in normal organs and highly expressed in tumors, so it is a potential target for diagnosis and treatment. Boronophenylalanine (BPA) is the most widely investigated BNCT drug in present. Compared with BPA, the boron content of a single molecule is increased and drug targeting is enhanced. The results show that Carboaren-FAPI has low toxicity to normal cells, and selective enrichment in tumor tissues. It is a promising boron drug that has the potential to be used in BNCT.
硼中子俘获治疗（BNCT）作为一种先进的二元放疗方法受到了广泛关注。然而，BNCT 仍然面临硼试剂选择性差和肿瘤组织中硼含量不足的问题。为了提高肿瘤靶向能力和硼含量，本研究旨在设计、合成并初步评价一种新型硼烷试剂 Carborane-FAPI，该试剂将 o--carborane 与成熟的成纤维细胞激活蛋白（FAP）抑制剂（FAPI）的化合物骨架偶联。FAP 是一种肿瘤相关抗原。FAP 在正常器官中低表达，在肿瘤中高表达，因此是诊断和治疗的潜在靶点。硼苯丙氨酸（BPA）是目前 BNCT 研究中应用最广泛的 BNCT 药物。与 BPA 相比，其单个分子的硼含量增加，药物靶向性增强。结果表明，Carboaren-FAPI 对正常细胞的毒性低，在肿瘤组织中有选择性富集。它是一种有前途的硼药物，有可能用于 BNCT。
