Skip to main content
Log in

Thoracoscopic Color and Fluorescence Imaging System for Sentinel Lymph Node Mapping in Porcine Lung Using Indocyanine Green-Neomannosyl Human Serum Albumin: Intraoperative Image-Guided Sentinel Nodes Navigation

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

This study was performed to validate a newly developed sentinel lymph node (SLN) targeting tracer, indocyanine green-neomannosyl human serum albumin (ICG:MSA), and a thoracoscopic version of the intraoperative color and fluorescence imaging system (ICFIS) for lung cancer SLN mapping.

Methods

ICG alone or ICG:MSA (5 μg/kg) was injected into the rat thigh, and the results were compared. The fluorescence signal-to-background ratios of SLNs were recorded and evaluated over a 2-h period by using ICFIS. Additionally, a SLN biopsy was performed via video-assisted thoracoscopic surgery with the use of ICG:MSA in porcine lung by using thoracoscopic ICFIS.

Results

The newly developed ICG:MSA showed a significantly improved signal-to-background ratio compared with ICG alone throughout the trials. All SLNs were identified in both rats (ten SLNs in ten rat thighs) and pigs (ten SLNs in ten porcine lungs) under in vivo conditions. All SLNs were dissected successfully by using video-assisted thoracoscopic surgery with the help of thoracoscopic ICFIS.

Discussion

ICG:MSA accumulates in the SLN by uptake and retention through the mannose-specific receptors on macrophages. Thoracoscopic ICFIS successfully assisted SLN mapping despite low near-infrared light transmission in the commercial thoracoscope. On the basis of the results of the thoracoscopic SLN mapping, we anticipate that ICG:MSA and thoracoscopic ICFIS can be translated to clinical trials in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

FIG. 1
FIG. 2
FIG. 3

Similar content being viewed by others

References

  1. Krag D, Weaver D, Alex J, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993;2:335–40.

    Article  CAS  PubMed  Google Scholar 

  2. Ross MI. Sentinel node biopsy for melanoma: an update after two decades of experience. Paper presented at Seminars in Cutaneous Medicine and Surgery 2010.

  3. Nomori H, Iwatani K, Kobayashi H, Mori A, Yoshioka S. Omission of mediastinal lymph node dissection in lung cancer: its techniques and diagnostic procedures. Ann Thorac Cardiovasc Surg. 2006;12:83–8.

    PubMed  Google Scholar 

  4. Hutteman M, Choi HS, Mieog JSD, et al. Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer using invisible near-infrared fluorescence light. Ann Surg Oncol. 2011;18:1006–14.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Yamauchi K, Nagafuji H, Nakamura T, Sato T, Kohno N. Feasibility of ICG fluorescence-guided sentinel node biopsy in animal models using the HyperEye Medical System. Ann Surg Oncol. 2011;18:2042–7.

    Article  PubMed  Google Scholar 

  6. Little AG, DeHoyos A, Kirgan DM, Arcomano TR, Murray KD. Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel node technique. J Thorac Cardiovasc Surg. 1999;117:220–4.

    Article  CAS  PubMed  Google Scholar 

  7. Liptay MJ, Masters GA, Winchester DJ, et al. Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer. Ann Thorac Surg. 2000;70:384–9.

    Article  CAS  PubMed  Google Scholar 

  8. Kim S, Kim HK, Kang D-Y, Jeong JM, Choi YH. Intra-operative sentinel lymph node identification using a novel receptor-binding agent (technetium-99m neomannosyl human serum albumin, 99mTc-MSA) in stage I non-small cell lung cancer. Eur J Cardiothorac Surg. 2010;37:1450–6.

    Article  PubMed  Google Scholar 

  9. Rzyman W, Hagen OM, Dziadziuszko R, et al. Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients. Ann Thorac Surg. 2006;82:237–42.

    Article  PubMed  Google Scholar 

  10. Liptay MJ, D’amico TA, Nwogu C, et al. Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial. J Thorac Oncol. 2009;4:198–202.

    Article  PubMed  Google Scholar 

  11. Sung HK. Comparison between preoperative versus intraoperative injection of technetium-99m neomannosyl human serum albumin for sentinel lymph node identification in early stage lung cancer. Ann Surg Oncol. 2012;19:1343–9.

    Article  PubMed  Google Scholar 

  12. Kim S, Lim YT, Soltesz EG, et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol. 2003;22:93–7.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Ashitate Y, Tanaka E, Stockdale A, Choi HS, Frangioni JV. Near-infrared fluorescence imaging of thoracic duct anatomy and function in open surgery and video-assisted thoracic surgery. J Thorac Cardiovasc Surg. 2011;142:31–8.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Yamashita S, Tokuishi K, Anami K, et al. Video-assisted thoracoscopic indocyanine green fluorescence imaging system shows sentinel lymph nodes in non-small-cell lung cancer. J Thorac Cardiovasc Surg. 2011;141:141–4.

    Article  PubMed  Google Scholar 

  15. Yamashita S, Tokuishi K, Miyawaki M, et al. Sentinel node navigation surgery by thoracoscopic fluorescence imaging system and molecular examination in non-small cell lung cancer. Ann Surg Oncol. 2012;19:728–33.

    Article  PubMed  Google Scholar 

  16. Matsui A, Tanaka E, Choi HS, et al. Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents. Surgery. 2010;148:87–95.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Oh Y, Quan YH, Choi Y, et al. Intraoperative combined color and fluorescent images-based sentinel node mapping in the porcine lung: comparison of indocyanine green with or without albumin premixing. J Thorac Cardiovasc Surg. 2013.

  18. Te Velde E, Veerman T, Subramaniam V, Ruers T. The use of fluorescent dyes and probes in surgical oncology. Eur J Surg Oncol. 2010;36:6–15.

    Article  Google Scholar 

  19. Troyan SL, Kianzad V, Gibbs-Strauss SL, et al. The FLARE™ intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in breast cancer sentinel lymph node mapping. Ann Surg Oncol. 2009;16:2943–52.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Hutteman M, Mieog JS, van der Vorst JR, et al. Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients. Breast Cancer Res Treat. 2011;127:163–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Kratz F, Warnecke A. Finding the optimal balance: challenges of improving conventional cancer chemotherapy using suitable combinations with nano-sized drug delivery systems. J Control Release. 2012;164:221–35.

    Article  CAS  PubMed  Google Scholar 

  22. Kratz F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release. 2008;132:171–83.

    Article  CAS  PubMed  Google Scholar 

  23. Ohnishi S, Lomnes SJ, Laurence RG, Gogbashian A, Mariani G, Frangioni JV. Organic alternatives to quantum dots for intraoperative near-infrared fluorescent sentinel lymph node mapping. Mol Imaging. 2005;4:172–81.

    PubMed  Google Scholar 

  24. Choi JY, Jeong JM, Yoo BC, et al. Development of Ga-68-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography. Nucl Med Biol. 2011;38:371–9.

    Article  CAS  PubMed  Google Scholar 

  25. Jeong JM, Hong MK, Kim YJ, et al. Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging. Nucl Med Commun. 2004;25:1211–7.

    Article  CAS  PubMed  Google Scholar 

  26. Polom K, Murawa D, Nowaczyk P, Rho Y, Murawa P. Breast cancer sentinel lymph node mapping using near infrared guided indocyanine green and indocyanine green-human serum albumin in comparison with gamma emitting radioactive colloid tracer. Eur J Surg Oncol. 2012;38:137–42.

    Article  CAS  PubMed  Google Scholar 

  27. van Dam GM, Themelis G, Crane LM, et al. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med. 2011;17:1315–9.

    Article  PubMed  Google Scholar 

  28. Saxena V, Sadoqi M, Shao J. Indocyanine green-loaded biodegradable nanoparticles: preparation, physicochemical characterization and in vitro release. Int J Pharm. 2004;278:293–301.

    Article  CAS  PubMed  Google Scholar 

  29. Proulx ST, Luciani P, Derzsi S, et al. Quantitative imaging of lymphatic function with liposomal indocyanine green. Cancer Res. 2010;70:7053–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Henze E, Schelbert H, Collins J, Najafi A, Barrio J, Bennett L. Lymphoscintigraphy with Tc-99m-labeled dextran. J Nucl Med. 1982;23:923–9.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by a Grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (No. A121074) and a National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science and Technology (No. 2012012166).

Disclosure

All intellectual property associated with thoracoscopic ICFIS is owned by Korea University. The authors have nothing to disclose with regard to commercial support.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Beop-Min Kim PhD or Hyun Koo Kim MD, PhD.

Additional information

Y. Oh and Y.S. Lee have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Video of intraoperative sentinel lymph node mapping by using thoracoscopic ICFIS in the porcine lung

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, Y., Lee, YS., Quan, Y.H. et al. Thoracoscopic Color and Fluorescence Imaging System for Sentinel Lymph Node Mapping in Porcine Lung Using Indocyanine Green-Neomannosyl Human Serum Albumin: Intraoperative Image-Guided Sentinel Nodes Navigation. Ann Surg Oncol 21, 1182–1188 (2014). https://doi.org/10.1245/s10434-013-3381-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-3381-z

Keywords

Navigation