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Evaluation of [(18)F]-CP18 as a PET Imaging Tracer for Apoptosis.
MedLine Citation:
PMID:  23681757     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Helen Su; Gang Chen; Umesh Gangadharmath; Luis F Gomez; Qianwa Liang; Fanrong Mu; Vani P Mocharla; A Katrin Szardenings; Joseph C Walsh; Chun-Fang Xia; Chul Yu; Hartmuth C Kolb
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-17
Journal Detail:
Title:  Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging     Volume:  -     ISSN:  1860-2002     ISO Abbreviation:  Mol Imaging Biol     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101125610     Medline TA:  Mol Imaging Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Molecular Imaging Biomarker Research, Siemens Medical Solutions USA, Inc, 6100 Bristol Parkway, Culver City, CA, 90230, USA.
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