title: Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer.
abstract: BACKGROUND
  Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.
  
  
  METHODS
  A small, portable version of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using (99m)Technetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM.
  
  
  RESULTS
  The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1-3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed.
  
  
  CONCLUSIONS
  We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Sven D
authors.initials: JS
authors.lastname: Mieog
authors.forename: Susan L
authors.initials: SL
authors.lastname: Troyan
authors.forename: Merlijn
authors.initials: M
authors.lastname: Hutteman
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Donohoe
authors.forename: Joost R
authors.initials: JR
authors.lastname: van der Vorst
authors.forename: Alan
authors.initials: A
authors.lastname: Stockdale
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Liefers
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: Summer L
authors.initials: SL
authors.lastname: Gibbs-Strauss
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gioux
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Ashitate
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: Rafiou
authors.initials: R
authors.lastname: Oketokoun
authors.forename: Long H
authors.initials: LH
authors.lastname: Ngo
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D018275:Carcinoma, Lobular / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D004396:Coloring Agents; D005260:Female; D005453:Fluorescence; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007208:Indocyanine Green; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D021701:Sentinel Lymph Node Biopsy; D019265:Spectroscopy, Near-Infrared; D013552:Swine
chemical_list: D004396:Coloring Agents; D019275:Radiopharmaceuticals; D007208:Indocyanine Green