title: Molecular imaging of Cathepsin E-positive tumors in mice using a novel protease-activatable fluorescent probe.
abstract: The purpose of this study is to demonstrate the ability of imaging Cathepsin E (Cath E) positive tumors in living animals through selective targeting of Cath E proteolytic activity using a sensitive molecular imaging agent.
  
  
  METHODS
  A peptide-based Cath E imaging probe and a control probe were synthesized for this study. Human Cath E-positive cancer cells (MPanc96-E) were implanted subcutaneously in nude mice. Tumor-bearing mice were examined in vivo with near-infrared fluorescence (NIRF) imaging at various time points after intravenous injection of the Cath E sensing imaging probe. Excised organs and tissues of interest were further imaged ex vivo.
  
  
  RESULTS
  Upon specific Cath E proteolytic activation, the NIRF signal of the imaging probe a was converted from an optically quenched initial state to a highly fluorescent active state. Imaging probe a was able to highlight the Cath E-positive tumors as early as 24 h post injection. Fluorescent signal in tumor was 3-fold higher than background. The confined specificity of imaging probe a to tumor associated Cath E was verified by using control imaging probe b. Both in vivo and ex vivo imaging results confirmed the superior selectivity and sensitivity of imaging probe a in Cath E imaging.
  
  
  CONCLUSIONS
  The small animal studies demonstrated the capability of probe a for imaging Cath E-positive tumors. The developed optical probe could be applied in early diagnostic imaging and guiding subsequent surgical procedure.
authors.affiliation: Department of Radiology, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, B5-009, Houston, TX 77030, USA.
authors.forename: Wael R
authors.initials: WR
authors.lastname: Abd-Elgaliel
authors.affiliation: Department of Cancer Biology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zobeida
authors.initials: Z
authors.lastname: Cruz-Monserrate
authors.affiliation: Department of Cancer Biology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.|Department of GI Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Logsdon
authors.affiliation: Department of Radiology, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, B5-009, Houston, TX 77030, USA.
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Tung
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D020059:Cathepsin E / Q000032:analysis*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D005456:Fluorescent Dyes; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000737:chemistry* / Q000175:diagnosis
chemical_list: D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D020059:Cathepsin E