2-Nitroimidazole-Tricarbocyanine Conjugate as a Near-Infrared Fluorescent Probe for in Vivo Imaging of Tumor Hypoxia

被引:153
作者
Okuda, Kensuke [1 ]
Okabe, Yasuyuki [1 ]
Kadonosono, Tetsuya [2 ]
Ueno, Takahiro [1 ]
Youssif, Bahaa G. M. [1 ]
Kizaka-Kondoh, Shinae [2 ]
Nagasawa, Hideko [1 ]
机构
[1] Gifu Pharmaceut Univ, Lab Pharmaceut & Med Chem, Gifu 5011196, Japan
[2] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Dept Biomol Engn, Yokohama, Kanagawa 2268501, Japan
基金
日本学术振兴会;
关键词
SOLID TUMORS; BINDING; CANCER; PIMONIDAZOLE; REGIONS;
D O I
10.1021/bc2004704
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We developed a novel near-infrared (NIR) fluorescent probe, GPU-167, for in vivo imaging of tumor hypcoda. GPU-167 comprises a tricarbocyanine dye as an NIR fluorophore and two 2-nitroimidazole moieties as exogenous hypoxia markers that undergo bioreductive activation and then selective entrapment in hypoxic cells. After treatment with GPU-167, tumor cells contained significantly higher levels of fluorescence in hypoxia than in normoxia. In vivo fluorescence imaging specifically detected GPU-167 in tumors 24 h after administration. Ex vivo analysis revealed that fluorescence showed a strong correlation with hypoxia inducible factor (HIF)-1 active hypoxic regions. These data suggest that GPU-167 is a promising in vivo optical imaging probe for tumor hypoxia.
引用
收藏
页码:324 / 329
页数:6
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