title: Surgical molecular navigation with ratiometric activatable cell penetrating peptide for intraoperative identification and resection of small salivary gland cancers.
abstract: BACKGROUND
  We evaluated the use of intraoperative fluorescence guidance by enzymatically cleavable ratiometric activatable cell-penetrating peptide (RACPPPLGC(Me)AG) containing Cy5 as a fluorescent donor and Cy7 as a fluorescent acceptor for salivary gland cancer surgery in a mouse model.
  
  
  METHODS
  Surgical resection of small parotid gland cancers in mice was performed with fluorescence guidance or white light (WL) imaging alone. Tumor identification accuracy, operating time, and tumor-free survival were compared.
  
  
  RESULTS
  RACPP guidance aided tumor detection (positive histology in 90% [27/30] vs 48% [15/31] for WL; p < .001). An approximate 25% ratiometric signal increase as the threshold to distinguish between tumor and adjacent tissue, yielded >90% detection sensitivity and specificity. Operating time was reduced by 54% (p < .001), and tumor-free survival was increased with RACPP guidance (p = .025).
  
  
  CONCLUSIONS
  RACPP provides real-time intraoperative guidance leading to improved survival. Ratiometric signal thresholds can be set according to desired detection accuracy levels for future RACPP applications.
authors.affiliation: Division of Head and Neck Surgery, University of California San Diego, San Diego, California.
authors.forename: Timon
authors.initials: T
authors.lastname: Hussain
authors.affiliation: Department of Pharmacology, University of California San Diego, San Diego, California.
authors.forename: Elamprakash N
authors.initials: EN
authors.lastname: Savariar
authors.affiliation: Division of Head and Neck Surgery, University of California San Diego, San Diego, California.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Diaz-Perez
authors.affiliation: Division of Biostatistics, Moores Cancer Center, University of California San Diego, San Diego, California.
authors.forename: Karen
authors.initials: K
authors.lastname: Messer
authors.affiliation: Division of Biostatistics, Moores Cancer Center, University of California San Diego, San Diego, California.
authors.forename: Minya
authors.initials: M
authors.lastname: Pu
authors.affiliation: Department of Pharmacology, University of California San Diego, San Diego, California.|Howard Hughes Medical Institute, University of California San Diego, San Diego, California.
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
authors.affiliation: Division of Head and Neck Surgery, University of California San Diego, San Diego, California.
authors.forename: Quyen T
authors.initials: QT
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D005260:Female; D005453:Fluorescence; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D061646:Operative Time; D012372:ROC Curve; D012468:Salivary Gland Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D025321:Surgery, Computer-Assisted / Q000379:methods
chemical_list: D057846:Cell-Penetrating Peptides
keywords: fluorescence-guided surgery; long-term survival; molecular imaging; molecular navigation; ratiometric activatable cell-penetrating peptide (RACPP)