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Evaluation of [(18)F]-CP18 as a PET imaging tracer for apoptosis
Helen Su1, Gang Chen, Umesh Gangadharmath
1Molecular Imaging Biomarker Research, Siemens Medical Solutions USA, Inc, 6100 Bristol Parkway, Culver City, CA, 90230, USA.
Purpose:
We identified and validated [(18)F]-CP18, a DEVD (the caspase 3 substrate recognition motif) containing substrate-based compound as an imaging tracer for caspase-3 activity in apoptotic cells.
Procedures:
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 [(18)F]-CP18 were assessed in vivo. [(18)F]-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.
Results:
In vitro enzymatic caspase-3 assay demonstrated specific cleavage of CP18. In vivo, [(18)F]-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 [(18)F]-CP18 retention in the dexamethasone-induced thymus of treated versus control mice.
Conclusions:
We report the use [(18)F]-CP18 as a PET tracer for imaging apoptosis. Our data support further development of this tracer for clinical PET applications.
