title: Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response in cancer.
abstract: OBJECTIVE
  We tested whether positron emission tomography (PET) with the caspase-3-targeted isatin analog [(18)F]WC-4-116 could image caspase-3 activation in response to an apoptosis-inducing anticancer therapy.
  
  
  METHODS
  [(18)F]WC-4-116 uptake was determined in etoposide-treated EL4 cells. Biodistribution studies with [(18)F]WC-4-116 and [(18)F]ICMT-18, a non-caspase-3-targeted tracer, as well as [(18)F]WC-4-116 microPET imaging assessed responses in Colo205 tumor-bearing mice treated with death receptor 5 (DR5)-targeted agonist antibodies. Immunohistochemical staining and enzyme assays confirmed caspase-3 activation. Two-way analysis of variance or Student's t test assessed for treatment-related changes in tracer uptake.
  
  
  RESULTS
  [(18)F]WC-4-116 increased 8 ± 2 fold in etoposide-treated cells. The [(18)F]WC-4-116 % ID/g also increased significantly in tumors with high caspase-3 enzyme activity (p < 0.05). [(18)F]ICMT-18 tumor uptake did not differ in tumors with high or low caspase-3 enzyme activity.
  
  
  CONCLUSIONS
  [(18)F]WC-4-116 uptake in vivo reflects increased caspase-3 activation and may be useful for detecting caspase-3-mediated apoptosis treatment responses in cancer.
authors.affiliation: Division of Radiological Sciences and Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway Blvd., St. Louis, MO, 63110, USA, chend@mir.wustl.edu.
authors.forename: Delphine L
authors.initials: DL
authors.lastname: Chen
authors.forename: Jacquelyn T
authors.initials: JT
authors.lastname: Engle
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Griffin
authors.forename: J Philip
authors.initials: JP
authors.lastname: Miller
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chu
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D007510:Isatin / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D013449:Sulfonamides; C000605615:WC-4-116; D007510:Isatin; D053148:Caspase 3; D053179:Caspase 7