Toward optimization of imaging system and lymphatic tracer for near-infrared fluorescent sentinel lymph node mapping in breast cancer

Ann Surg Oncol. 2011 Sep;18(9):2483-91. doi: 10.1245/s10434-011-1566-x. Epub 2011 Mar 1.

Abstract

Background: Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.

Materials and 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.

Trial registration: ClinicalTrials.gov NCT00721370.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / diagnostic imaging*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / surgery
  • Carcinoma, Intraductal, Noninfiltrating / diagnostic imaging*
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Carcinoma, Intraductal, Noninfiltrating / surgery
  • Carcinoma, Lobular / diagnostic imaging*
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / surgery
  • Coloring Agents
  • Female
  • Fluorescence
  • Humans
  • Image Processing, Computer-Assisted
  • Indocyanine Green
  • Lymph Nodes
  • Lymphatic Metastasis
  • Lymphatic Vessels / diagnostic imaging*
  • Lymphatic Vessels / pathology
  • Lymphatic Vessels / surgery
  • Middle Aged
  • Pilot Projects
  • Prognosis
  • Radionuclide Imaging
  • Radiopharmaceuticals
  • Sentinel Lymph Node Biopsy
  • Spectroscopy, Near-Infrared
  • Swine

Substances

  • Coloring Agents
  • Radiopharmaceuticals
  • Indocyanine Green

Associated data

  • ClinicalTrials.gov/NCT00721370