多塔
化学
体内分布
放射化学
肽
共轭体系
硼
中子俘获
组合化学
体外
螯合作用
生物化学
有机化学
聚合物
作者
Kenji Mishiro,Satoshi Imai,Yuki Ematsu,Katsumi Hirose,Takeshi Fuchigami,Masayuki Munekane,Seigo Kinuya,Kenji Ogawa
标识
DOI:10.1021/acs.jmedchem.2c01586
摘要
A boron neutron capture therapy (BNCT) system, using boron-10-introduced agents coupled with companion diagnostics, is anticipated as a promising cancer theranostic. Thus, this study aimed to synthesize and evaluate a probe closo-dodecaborate-(Ga-DOTA)-c(RGDfK) (16) [Ga = gallium, DOTA =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, and c(RGDfK) = cyclo(arginine-glycine-aspartate-d-phenylalanine-lysine] containing closo-dodecaborate ([B12H12]2-) as a boron cluster, a [67Ga]Ga-DOTA derivative for nuclear medicine imaging, and an RGD peptide for tumor targeting. Moreover, we prepared a radioiodinated probe [125I]17 in which I-125 is introduced into a closo-dodecaborate moiety of 16. [67Ga]16 and [125I]17 showed high stability and high uptake in cancer cells in vitro. Biodistribution experiments in tumor-bearing mice revealed similar biodistribution patterns between [67Ga]16 and [125I]17, such as a high uptake in the tumor and a low uptake in other non-target tissues. Meanwhile, [125I]17 exhibited higher accumulation in most tissues, including the tumor, than [67Ga]16, probably because of higher albumin binding. The higher the [125I]17 accumulation in the tumor, the more desirable it is for BNCT, with the possibility that the iodo-closo-dodecaborate site may work as an albumin binder.
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