Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 24, Pages 8057-8067Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm801107u
Keywords
-
Categories
Funding
- 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
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available