title: Evaluation of [(18)F]-CP18 as a PET imaging tracer for apoptosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Molecular Imaging Biomarker Research, Siemens Medical Solutions USA, Inc, 6100 Bristol Parkway, Culver City, CA, 90230, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Su
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Umesh
authors.initials: U
authors.lastname: Gangadharmath
authors.forename: Luis F
authors.initials: LF
authors.lastname: Gomez
authors.forename: Qianwa
authors.initials: Q
authors.lastname: Liang
authors.forename: Fanrong
authors.initials: F
authors.lastname: Mu
authors.forename: Vani P
authors.initials: VP
authors.lastname: Mocharla
authors.forename: A Katrin
authors.initials: AK
authors.lastname: Szardenings
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Walsh
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Xia
authors.forename: Chul
authors.initials: C
authors.lastname: Yu
authors.forename: Hartmuth C
authors.initials: HC
authors.lastname: Kolb
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000009:adverse effects; D006020:Glycopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D016014:Linear Models; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D013950:Thymus Gland / Q000737:chemistry / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: C586095:CP-18 compound; D006020:Glycopeptides; D019275:Radiopharmaceuticals; D003907:Dexamethasone; D053148:Caspase 3