Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer

Br J Surg. 2013 Jul;100(8):1037-44. doi: 10.1002/bjs.9159. Epub 2013 May 21.


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.

Conclusion: The hybrid NIR fluorescence and radioactive tracer permitted accurate preoperative and intraoperative detection of the SLNs in patients with breast cancer.

Registration number: NTR3685 (Netherlands Trial Register;

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast / pathology*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / diagnostic imaging
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / diagnostic imaging
  • Carcinoma, Lobular / pathology*
  • Coloring Agents
  • Female
  • Fluorescence
  • Humans
  • Image-Guided Biopsy
  • Indocyanine Green
  • Intraoperative Care / methods
  • Lymphatic Metastasis
  • Lymphoscintigraphy / methods
  • Middle Aged
  • Radiopharmaceuticals
  • Sentinel Lymph Node Biopsy / methods
  • Spectroscopy, Near-Infrared
  • Technetium Tc 99m Aggregated Albumin


  • Coloring Agents
  • Radiopharmaceuticals
  • Technetium Tc 99m Aggregated Albumin
  • technetium Tc 99m nanocolloid
  • Indocyanine Green