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

Hyun Koo Kim, Yujin Oh, Ji Yong Park, Ji Ho Park, Yeonho Choi, Yeonho Choi, Jae Min Jeong, Young Ho Choi, Young Ho Choi, Beop-Min Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish
JournalAnnals of Thoracic Surgery
DOIs
Publication statusAccepted/In press - 2016

Fingerprint

Indocyanine Green
Serum Albumin
Esophagus
Swine
Macrophages
Sentinel Lymph Node
Optical Imaging
Esophageal Neoplasms
Rabbits
Lymphatic System
U937 Cells
Injections

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Macrophage-Targeted Indocyanine Green-Neomannosyl Human Serum Albumin for Intraoperative Sentinel Lymph Node Mapping in Porcine Esophagus. / Kim, Hyun Koo ; Oh, Yujin; Park, Ji Yong; Park, Ji Ho; Choi, Yeonho; Choi, Yeonho; Jeong, Jae Min; Choi, Young Ho; Choi, Young Ho; Kim, Beop-Min.

In: Annals of Thoracic Surgery, 2016.

Research output: Contribution to journalArticle

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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. Conclusion: 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.",
author = "Kim, {Hyun Koo} and Yujin Oh and Park, {Ji Yong} and Park, {Ji Ho} and Yeonho Choi and Yeonho Choi and Jeong, {Jae Min} and Choi, {Young Ho} and Choi, {Young Ho} and Beop-Min Kim",
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T1 - Macrophage-Targeted Indocyanine Green-Neomannosyl Human Serum Albumin for Intraoperative Sentinel Lymph Node Mapping in Porcine Esophagus

AU - Kim, Hyun Koo

AU - Oh, Yujin

AU - Park, Ji Yong

AU - Park, Ji Ho

AU - Choi, Yeonho

AU - Choi, Yeonho

AU - Jeong, Jae Min

AU - Choi, Young Ho

AU - Choi, Young Ho

AU - Kim, Beop-Min

PY - 2016

Y1 - 2016

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

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