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Updated: Jun 27, 2026
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Design, synthesis, and biological characterization of a caspase 3/7 selective isatin labeled with
Graham Smith1, Matthias Glaser, Meg Perumal
1Molecular Therapy Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
Abstract:
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.
Insights
Researchers developed a novel 18F-labeled isatin sulfonamide for imaging apoptosis. This new radiotracer shows high stability and affinity for caspase 3/7, making it promising for preclinical cancer and disease diagnosis.
Area of Science:
- Radiochemistry
- Molecular Imaging
- Oncology
Background:
- Imaging programmed cell death (apoptosis) is crucial for assessing cancer therapy response and diagnosing cardiac/neurodegenerative disorders.
- Executioner caspases 3 and 7 are key targets for in vivo apoptosis quantification.
Purpose of the Study:
- Develop 18F-labeled isatin sulfonamides for apoptosis imaging.
- Achieve high metabolic stability, moderate lipophilicity, and selectivity for caspase 3/7.
Main Methods:
- Synthesized a library of isatins with fluorinated aromatic groups and heterocycles.
- Identified a lead compound with subnanomolar affinity for caspase 3.
- Utilized "click labeling" with 2-[18F]fluoroethylazide for radiotracer synthesis.
Main Results:
- Developed a novel 18F-labeled isatin sulfonamide with high affinity for caspase 3.
- Achieved 65% decay-corrected radiochemical yield using "click labeling".
- Demonstrated high in vivo stability with rapid uptake/elimination in healthy tissues and tumors.
Conclusions:
- The novel 18F-labeled isatin sulfonamide is a promising candidate radiotracer.
- Further preclinical evaluation is warranted for apoptosis imaging in oncology and other disorders.
