title: Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer.
abstract: BACKGROUND
  Combining radioactive colloids and a near-infrared (NIR) fluorophore permits preoperative planning and intraoperative localization of deeply located sentinel lymph nodes (SLNs) with direct optical guidance by a single lymphatic tracer. The aim of this clinical trial was to evaluate and optimize a hybrid NIR fluorescence and radioactive tracer for SLN detection in patients with breast cancer.
  
  
  METHODS
  Patients with breast cancer undergoing SLN biopsy were enrolled. The day before surgery, a periareolar injection of indocyanine green (ICG)-99mTc-radiolabelled nanocolloid was administered and a lymphoscintigram acquired. Blue dye was injected immediately before surgery. Intraoperative SLN localization was performed using a γ probe and the Mini-FLARE™ NIR fluorescence imaging system. Patients were divided into two dose groups, with one group receiving twice the particle density of ICG and nanocolloid, but the same dose of radioactive 99mTc.
  
  
  RESULTS
  Thirty-two patients were enrolled in the trial. At least one SLN was identified before and during operation. All 48 axillary SLNs could be detected by γ tracing and NIR fluorescence imaging, but only 42 of them stained blue. NIR fluorescence imaging permitted detection of lymphatic vessels draining to the SLN up to 29 h after injection. Doubling the particle density did not yield a difference in fluorescence intensity (median 255 (range 98-542) versus 284 (90-921) arbitrary units; P = 0.590) or signal-to-background ratio (median 5·4 (range 3·0-15·4) versus 4·9 (3·5-16·3); P = 1·000) of the SLN.
  
  
  CONCLUSIONS
  The hybrid NIR fluorescence and radioactive tracer permitted accurate preoperative and intraoperative detection of the SLNs in patients with breast cancer.
  
  
  BACKGROUND
  NTR3685 (Netherlands Trial Register; http://www.trialregister.nl).
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: B E
authors.initials: BE
authors.lastname: Schaafsma
authors.forename: F P R
authors.initials: FP
authors.lastname: Verbeek
authors.forename: D D D
authors.initials: DD
authors.lastname: Rietbergen
authors.forename: B
authors.initials: B
authors.lastname: van der Hiel
authors.forename: J R
authors.initials: JR
authors.lastname: van der Vorst
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.forename: J V
authors.initials: JV
authors.lastname: Frangioni
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: F W B
authors.initials: FW
authors.lastname: van Leeuwen
authors.forename: A L
authors.initials: AL
authors.lastname: Vahrmeijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000000981:diagnostic imaging / Q000473:pathology*; D004396:Coloring Agents; D005260:Female; D005453:Fluorescence; D006801:Humans; D061705:Image-Guided Biopsy; D007208:Indocyanine Green; D007430:Intraoperative Care / Q000379:methods; D008207:Lymphatic Metastasis; D061305:Lymphoscintigraphy / Q000379:methods; D008875:Middle Aged; D019275:Radiopharmaceuticals; D021701:Sentinel Lymph Node Biopsy / Q000379:methods; D019265:Spectroscopy, Near-Infrared; D013668:Technetium Tc 99m Aggregated Albumin
chemical_list: D004396:Coloring Agents; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C083602:technetium Tc 99m nanocolloid; D007208:Indocyanine Green