A Boronate-Caged [18F]FLT Probe for Hydrogen Peroxide Detection Using Positron Emission Tomography

被引:110
作者
Carroll, Valerie [1 ]
Michel, Brian W. [2 ,3 ,4 ]
Blecha, Joseph [1 ]
VanBrocklin, Henry [1 ]
Keshari, Kayvan [5 ,6 ]
Wilson, David [1 ]
Chang, Christopher J. [2 ,3 ,4 ]
机构
[1] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94158 USA
[2] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[5] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA
[6] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA
关键词
OXIDATIVE STRESS; IN-VIVO; FLUORESCENT-PROBES; MECHANISMS; TRANSPORT; BIOLOGY; CANCER; DYSFUNCTION; SUPEROXIDE; MOLECULES;
D O I
10.1021/ja509198w
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
ive oxygen species (ROS) play important roles in the development and progression of cancer and other diseases, motivating the development of translatable technologies for biological ROS imaging. Here we report Peroxy-Caged-[F-18]Fluorodeoxy thymidine-1 (PC-FLT-1), an oxidatively immolative positron emission tomography (PET) probe for H2O2 detection. PC-FLT-1 reacts with H2O2 to generate [F-18]FLT, allowing its peroxide-dependent uptake and retention in proliferating cells. The relative uptake of PC-FLT-1 was evaluated using H2O2-treated UOK262 renal carcinoma cells and a paraquat-induced oxidative stress cell model, demonstrating ROS-dependent tracer accumulation. The data suggest that PC-FLT-1 possesses promising characteristics for translatable ROS detection and provide a general approach to PET imaging that can be expanded to the in vivo study of other biologically relevant analytes.
引用
收藏
页码:14742 / 14745
页数:4
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