title: Image-guided oncologic surgery using invisible light: completed pre-clinical development for sentinel lymph node mapping.
abstract: BACKGROUND
  Invisible near-infrared (NIR) fluorescent light permits high sensitivity, real-time image-guidance during oncologic surgery without changing the look of the surgical field. In this study, we complete pre-clinical development of the technology for sentinel lymph node (SLN) mapping using a large animal model of spontaneous melanoma.
  
  
  METHODS
  Sinclair swine with spontaneous melanoma metastatic to regional lymph nodes were used because of their similarity to human melanoma. Organic lymphatic tracers tested included FDA-approved indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic hybrid tracer tested was type II NIR quantum dots with an anionic coating. Primary tumors received four peri-tumoral injections of each tracer, with a fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image-guided resection were performed in real-time.
  
  
  RESULTS
  Each of the 3 lymphatic tracers was injected into n = 4 separate primary melanomas in a total of 6 animals. All 12 injections resulted in identification of the SLN(s) and their associated lymphatic channels within 1 minute in 100% of cases, despite highly pigmented skin and black fur. Hydrodynamic diameter had a profound impact on tracer behavior in vivo.
  
  
  CONCLUSIONS
  This study completes the pre-clinical development of NIR fluorescence-guided SLN mapping and provides insight into imaging system optimization and tracer choice for future human clinical trials. The technology is likely to eliminate the need for radioactive and colored tracers, permits real-time image guidance throughout the procedure, and assists the pathologist in tissue analysis.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tanaka
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Moungi G
authors.initials: MG
authors.lastname: Bawendi
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000493:pharmacokinetics; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007432:Intraoperative Period; D008027:Light; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000556:secondary / Q000601:surgery*; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D012878:Skin Neoplasms / Q000473:pathology / Q000601:surgery*; D019265:Spectroscopy, Near-Infrared; D025321:Surgery, Computer-Assisted; D034421:Sus scrofa
chemical_list: D004396:Coloring Agents; D005456:Fluorescent Dyes