Macrophage-Targeted Indocyanine Green-Neomannosyl Human Serum Albumin for Intraoperative Sentinel Lymph Node Mapping in Porcine Esophagus

Ann Thorac Surg. 2016 Oct;102(4):1149-55. doi: 10.1016/j.athoracsur.2016.04.077. Epub 2016 Jun 25.

Abstract

Background: The sentinel lymph node (SLN) concept has been proposed to avoid unnecessary invasive LN dissection in surgery for esophageal cancer. This study evaluated a new macrophage-targeting fluorescent agent, indocyanine green-neomannosyl human serum albumin (ICG:MSA), for SLN mapping using a custom-made intraoperative color and fluorescence-merged imaging system (ICFIS) in porcine esophagus.

Methods: The LN targeting ability of ICG:MSA, indocyanine green-human serum albumin (ICG:HSA), and ICG was examined in vitro using the U937 differentiated monocyte cell line and in vivo in a mouse footpad model using fluorescence imaging. SLN identification in rabbit esophagus was then performed using ICG:MSA, ICG:HSA, and ICG. Finally, intraoperative SLN detection was conducted in porcine esophagus after esophagoscopic injection of ICG:MSA.

Results: The fluorescence signal of U937 cells treated by ICG:MSA was significantly higher than that of ICG or ICG:HSA (ICG: 1.0 ± 0.37; ICG:HSA: 3.4 ± 0.28, ICG:MSA: 6.8 ± 1.61; ICG to ICG:HSA, p = 0.03; ICG:HSA to ICG:MSA, p = 0.04; ICG to ICG:MSA, p = 0.0009). ICG:MSA was retained in popliteal LNs as long as 3 h, while ICG rapidly diffused through the entire mouse lymphatic system within 5 min. Esophageal SLN was detected within 15 min after injection of either ICG or ICG:MSA, but ICG:MSA provided more distinguishable images of LNss than ICG in rabbit esophagus. The SLN was also successfully detected in all porcine esophagus; the mean number of SLNs identified per esophagus was 1.6 ± 0.55.

Conclusions: ICG:MSA has more specific macrophage-targeting properties, which could overcome the limitation of the low SLN retention of ICG, and could provide more precise real-time SLN detection during esophageal cancer surgery.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Coloring Agents / pharmacology
  • Disease Models, Animal
  • Drug Delivery Systems / methods
  • Esophagus / diagnostic imaging*
  • Esophagus / pathology
  • Esophagus / surgery*
  • Female
  • Fluorescence*
  • Indocyanine Green / pharmacology*
  • Macrophages
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Monitoring, Intraoperative / methods
  • Rabbits
  • Random Allocation
  • Sentinel Lymph Node / diagnostic imaging*
  • Sentinel Lymph Node / pathology
  • Sentinel Lymph Node Biopsy
  • Swine

Substances

  • Coloring Agents
  • Indocyanine Green