Evaluation of [18F]-CP18 as a PET Imaging Tracer for Apoptosis

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 selectivi...

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Published in:Molecular imaging and biology 2013-12, Vol.15 (6), p.739-747
Main Authors: Su, Helen, Chen, Gang, Gangadharmath, Umesh, Gomez, Luis F., Liang, Qianwa, Mu, Fanrong, Mocharla, Vani P., Szardenings, A Katrin, Walsh, Joseph C., Xia, Chun-Fang, Yu, Chul, Kolb, Hartmuth C.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Apoptosis
Caspase 3 - metabolism
Cell Line, Tumor
Dexamethasone - adverse effects
Glycopeptides - chemistry
Glycopeptides - pharmacokinetics
Humans
Imaging
Linear Models
Medicine
Medicine & Public Health
Mice
Molecular Imaging - methods
Positron-Emission Tomography - methods
Radiology
Radiopharmaceuticals - chemistry
Radiopharmaceuticals - pharmacokinetics
Research Article
Thymus Gland - chemistry
Thymus Gland - drug effects
Tissue Distribution
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Summary: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.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-013-0644-9