期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 51, 期 24, 页码 8057-8067出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm801107u
关键词
-
资金
- Cancer Research UK programme [C2536/A5708]
- UK Medical Research Council [U.1200.02.005.00001.01]
- Medical Research Council [MC_U120081322] Funding Source: researchfish
- MRC [MC_U120081322] Funding Source: UKRI
Imaging of programmed cell death (apoptosis) is important in the assessment of therapeutic response in oncology and for diagnosis in cardiac and neurodegenerative disorders. The executioner caspases 3 and 7 ultimately effect cellular death, thus providing selective molecular targets for in vivo quantification of apoptosis. To realize this potential, we aimed to develop F-18-labeled isatin sulfonamides with high metabolic,stability and moderate lipophilicity while retaining selectivity and affinity for caspase 3/7. A small library of isatins modified with fluorinated aromatic groups and heterocycles was synthesized. A lead compound incorporating 2'-fluoroethyl-1,2,3-triazole was identified with subnanomolar affinity for caspase 3. Click labeling provided the F-18-labeled tracer in 65 +/- 6% decay-corrected radiochemical yield from 2-[F-18]fluoroethylazide. The compound showed high stability in vivo with rapid uptake and elimination in healthy tissues and tumor. The novel F-18-labeled isatin is a candidate radiotracer for further preclinical evaluation for imaging of apoptosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据