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J Med Chem. 2008 Dec 25;51(24):8057-67. doi: 10.1021/jm801107u.

Design, synthesis, and biological characterization of a caspase 3/7 selective isatin labeled with 2-[18F]fluoroethylazide.

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Molecular Therapy Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.


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 18F-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 18F-labeled tracer in 65 +/- 6% decay-corrected radiochemical yield from 2-[18F]fluoroethylazide. The compound showed high stability in vivo with rapid uptake and elimination in healthy tissues and tumor. The novel 18F-labeled isatin is a candidate radiotracer for further preclinical evaluation for imaging of apoptosis.

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