Evaluation of [18F]-CP18 as a PET Imaging Tracer for Apoptosis
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We identified and validated [18F]-CP18, a DEVD (the caspase 3 substrate recognition motif) containing substrate-based compound as an imaging tracer for caspase-3 activity in apoptotic cells.
CP18 was radiolabeled with fluorine-18 using click chemistry. The affinity and selectivity of CP18 for caspase-3 were evaluated in vitro. The biodistribution and metabolism pattern of [18F]-CP18 were assessed in vivo. [18F]-CP18 positron emission tomography (PET) scans were performed in a dexamethasone-induced thymic apoptosis mouse model. After imaging, the mice were sacrificed, and individual organs were collected, measured in a gamma counter, and tested for caspase-3 activity.
In vitro enzymatic caspase-3 assay demonstrated specific cleavage of CP18. In vivo, [18F]-CP18 is predominantly cleared through the kidneys and urine, and is rapidly eliminated from the bloodstream. There was a sixfold increase in caspase activity and a fourfold increase of [18F]-CP18 retention in the dexamethasone-induced thymus of treated versus control mice.
We report the use [18F]-CP18 as a PET tracer for imaging apoptosis. Our data support further development of this tracer for clinical PET applications.
Key wordsApoptosis Molecular imaging PET Caspase
We thank Dr. Kai Chen for contributing to the design of CP18. We thank James Secrest and Janna Arteaga for facilitating the animal experiments.
Conflict of Interest
The authors declare that they have no conflict of interest.
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