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

Abstract

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 (99m) technetium-nancolloid and patent blue. In addition, intraoperative NIR fluorescence imaging was performed after injection of 1·6 mL of 600, 800, 1000 or 1200 μmolL(-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 (P=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 μmolL(-1) appears optimal for SLN mapping in cutaneous melanoma, although lower doses need to be assessed.

Figure 1. Sentinel lymph node mapping using NIR fluorescence imaging in cutaneous melanoma

Lymphatic channel (arrowhead) and SLNs (arrows) can be clearly identified percutaneously (top row). Identification of the first SLN (middle row) and second SLN (bottom row) is demonstrated using NIR fluorescence imaging at 15 min after injection of 1.6 mL of 1000 μM ICG:HSA around the excision scar.

Figure 2. Optimization of ICG:HSA dose

Signal-to-background ratio (mean ± S.D.) of melanoma SLNs (ordinate) is plotted as a function of injected dose of ICG:HSA (abscissa). A trend was found favouring the 600, 800 and 1000 μM over 1200 μM (P = 0.066).