title: Molecular targeting of papillary thyroid carcinoma with fluorescently labeled ratiometric activatable cell penetrating peptides in a transgenic murine model.
abstract: OBJECTIVE
  Molecularly targeted fluorescent molecules may help detect tumors that are unseen by traditional white-light surgical techniques. We sought to evaluate a fluorescent ratiometric activatable cell penetrating peptide (RACPP) for tumor detection in a transgenic model of PTC.
  
  
  METHODS
  Thirteen BRAFV600E mice with PTC were studied-seven injected intravenously with RACPP, four controls with saline. Total thyroidectomy was performed with microscopic white-light visualization. Fluorescent imaging of post-thyroidectomy fields was performed, and tissue with increased signal was removed and evaluated for PTC. Final samples were analyzed by a pathologist blinded to conditions. Vocal cord function was evaluated postoperatively with video laryngoscopy.
  
  
  RESULTS
  The average in situ ratiometric (Cy5/Cy7) thyroid tumor-to-background contrast ratio was 2.27 +/- 0.91. Fluorescence-guided clean-up following thyroidectomy identified additional tumor in 2 of 7 RACPP animals (smallest dimension 1.2 mm), and decreased the number of animals with residual tumor from 4 to 3. All retained tumor foci on final pathology were smaller than 0.76 mm. Intact vocal abduction was present in all of the RACPP animals.
  
  
  CONCLUSIONS
  RACPPs successfully targeted PTC in a transgenic thyroidectomy model, and allowed for residual tumor detection that reduced positive margins beyond what was possible with white-light surgery alone.
authors.affiliation: Department of Surgery, Division of Head and Neck Surgery, University of California San Diego, San Diego, California.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Orosco
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: Department of Surgery, Division of Head and Neck Surgery, University of California San Diego, San Diego, California.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Weissbrod
authors.affiliation: Department of Pathology, Moores Cancer Center, University of California San Diego, La Jolla, California.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Diaz-Perez
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of California San Diego, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
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: Department of Surgery, 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; D030801:Animals, Genetically Modified; D002277:Carcinoma / Q000235:genetics / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D002291:Carcinoma, Papillary; D057846:Cell-Penetrating Peptides; D004195:Disease Models, Animal; D005453:Fluorescence; D018698:Glutamic Acid; D007828:Laryngoscopy; D007830:Larynx / Q000503:physiopathology; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013194:Staining and Labeling; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D013965:Thyroidectomy / Q000379:methods; D016896:Treatment Outcome; D014633:Valine; D014741:Video Recording; D014827:Vocal Cords / Q000503:physiopathology
chemical_list: D057846:Cell-Penetrating Peptides; D018698:Glutamic Acid; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine
keywords: BRAF V600E; activatable cell penetrating peptide; laryngoscopy; murine model; papillary thyroid cancer; surgical molecular guidance