title: In vitro and in vivo evaluation of the caspase-3 substrate-based radiotracer [(18)F]-CP18 for PET imaging of apoptosis in tumors.
abstract: OBJECTIVE
  A novel caspase-3 substrate-based probe [(18)F]-CP18 was evaluated as an in vivo positron emission tomography (PET) imaging agent for monitoring apoptosis in tumors.
  
  
  METHODS
  Uptake of [(18)F]-CP18 in cell assays and tumors was measured. Caspase-3/7 activities in cell lysates and tumor homogenates were determined. Autoradiography,Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and cleaved caspase-3 immunostaining were performed on adjacent tumor sections to identify areas of apoptosis.
  
  
  RESULTS
  The in vitro cell assays showed caspase-3-dependent uptake of [(18)F]-CP18 in tumor cells when treated with an apoptosis inducer. The in vivo microPET imaging signal of [(18)F]-CP18 in xenograft tumors correlated with the ex vivo caspase-3/7 activities in these tumors. Furthermore, tumor autoradiographies of [(18)F]-CP18 in tumor sections matched adjacent sections stained by TUNEL and caspase-3 immunohistochemistry (IHC).
  
  
  CONCLUSIONS
  [(18)F]-CP18 demonstrated high affinity and selectivity for activated caspase-3 both in vitro and in vivo, and the results support [(18)F]-CP18 as a promising new PET imaging agent for apoptosis.
authors.affiliation: Molecular Imaging Biomarker Research, Siemens Medical Solutions USA, Inc., 6100 Bristol Parkway, Culver City, CA, 90230, USA.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Xia
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: Helen
authors.initials: H
authors.lastname: Su
authors.forename: A Katrin
authors.initials: AK
authors.lastname: Szardenings
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Walsh
authors.forename: Tieming
authors.initials: T
authors.lastname: Zhao
authors.forename: Hartmuth C
authors.initials: HC
authors.lastname: Kolb
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D053179:Caspase 7 / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D006020:Glycopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D016014:Linear Models; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C586095:CP-18 compound; D006020:Glycopeptides; D019275:Radiopharmaceuticals; D053148:Caspase 3; D053179:Caspase 7