Dose optimization for near-infrared fluorescence sentinel lymph node mapping in patients with melanoma


  • Funding sources
    This work was supported in part by NIH grants R01-CA-115296 and R21-CA-130297 and the Dutch Cancer Society grant UL2010-4732. This research was performed within the framework of CTMM, the Center for Translational Molecular Medicine, project MUSIS (grant 03O-202). J.R.v.d.V. is an MD-medical research trainee funded by the Netherlands Organisation for Health Research and Development (grant 92003593).

  • Conflicts of interest
    FLARE™ technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. It has been licensed to the FLARE™ Foundation, a non-profit organization focused on promoting the dissemination of medical imaging technology for research and clinical use. J.V.F. is the founder and chairman of the FLARE™ Foundation. The Beth Israel Deaconess Medical Center will receive royalties for sale of FLARE™ Technology. J.V.F. has elected to surrender post-market royalties to which he would otherwise be entitled as inventor, and has elected to donate pre-market proceeds to the FLARE™ Foundation.

  • The first two authors contributed equally to the study and share first authorship.

Alexander L. Vahrmeijer.


Background  Regional lymph node involvement is the most important prognostic factor in cutaneous melanoma. As only 20% of patients with melanoma have occult nodal disease and would benefit from a regional lymphadenectomy, the sentinel lymph node (SLN) biopsy was introduced. Near-infrared (NIR) fluorescence has been hypothesized to improve SLN mapping.

Objectives  To assess the potential of intraoperative NIR fluorescence imaging to improve SLN mapping in patients with melanoma and to examine the optimal dose of indocyanine green adsorbed to human serum albumin (ICG:HSA).

Methods  Fifteen consecutive patients with cutaneous melanoma underwent the standard SLN procedure using 99mtechnetium-nancolloid and patent blue. In addition, intraoperative NIR fluorescence imaging was performed after injection of 1·6 mL of 600, 800, 1000 or 1200 μmol L−1 of ICG:HSA in four quadrants around the primary excision scar.

Results  NIR fluorescence SLN mapping was successful in 93% of patients. In one patient, no SLN could be identified using either conventional methods or NIR fluorescence. A total of 30 SLNs (average 2·0, range 1–7) were detected, 30 radioactive (100%), 27 blue (73%) and 30 NIR fluorescent (100%). With regard to the effect of concentration on signal-to-background ratios a trend (= 0·066) was found favouring the 600, 800 and 1000 μmol L−1 groups over the 1200 μmol L−1 group.

Conclusion  This study demonstrates feasibility and accuracy of SLN mapping using ICG:HSA. Considering safety, cost and pharmacological characteristics, an ICG:HSA concentration of 600 μmol L−1 appears optimal for SLN mapping in cutaneous melanoma, although lower doses need to be assessed.