title: Macrophage-Targeted Indocyanine Green-Neomannosyl Human Serum Albumin for Intraoperative Sentinel Lymph Node Mapping in Porcine Esophagus.
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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Hyun Koo
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Yu Hua
authors.initials: YH
authors.lastname: Quan
authors.affiliation: Department of Bio-convergence Engineering, School of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea; Future IT R&D Laboratory, LG Electronics, Seoul, Korea.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Bio-convergence Engineering, School of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea.
authors.forename: Yeonho
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Bio-convergence Engineering, School of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea. Electronic address: bmk515@korea.ac.kr.
authors.forename: Beop-Min
authors.initials: BM
authors.lastname: Kim
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D004947:Esophagus / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*; D005260:Female; D005453:Fluorescence; D007208:Indocyanine Green / Q000494:pharmacology*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016343:Monitoring, Intraoperative / Q000379:methods; D011817:Rabbits; D011897:Random Allocation; D000071036:Sentinel Lymph Node / Q000000981:diagnostic imaging* / Q000473:pathology; D021701:Sentinel Lymph Node Biopsy; D013552:Swine
chemical_list: D004396:Coloring Agents; D007208:Indocyanine Green