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Image-Guided Oncologic Surgery Using Invisible Light: Completed Pre-Clinical Development for Sentinel Lymph Node Mapping

Abstract

Background

Invisible near-infrared (NIR) fluorescent light permits high sensitivity, real-time image-guidance during oncologic surgery without changing the look of the surgical field. In this study, we complete pre-clinical development of the technology for sentinel lymph node (SLN) mapping using a large animal model of spontaneous melanoma.

Methods

Sinclair swine with spontaneous melanoma metastatic to regional lymph nodes were used because of their similarity to human melanoma. Organic lymphatic tracers tested included FDA-approved indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic hybrid tracer tested was type II NIR quantum dots with an anionic coating. Primary tumors received four peri-tumoral injections of each tracer, with a fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image-guided resection were performed in real-time.

Results

Each of the 3 lymphatic tracers was injected into n = 4 separate primary melanomas in a total of 6 animals. All 12 injections resulted in identification of the SLN(s) and their associated lymphatic channels within 1 minute in 100% of cases, despite highly pigmented skin and black fur. Hydrodynamic diameter had a profound impact on tracer behavior in vivo.

Conclusions

This study completes the pre-clinical development of NIR fluorescence-guided SLN mapping and provides insight into imaging system optimization and tracer choice for future human clinical trials. The technology is likely to eliminate the need for radioactive and colored tracers, permits real-time image guidance throughout the procedure, and assists the pathologist in tissue analysis.

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Acknowledgments

We thank Rita G. Laurence for assistance with animal anesthesia, Alec M. De Grand for maintenance of imaging system software, Daniel A. Brown for cryo-sectioning, Barbara L. Clough for editing, and Grisel Vasquez for administrative assistance. This work was supported in part by the National Science Foundation-Materials Research Science and Engineering Center Program under grant DMR-0213282 (MGB), NIH grants #R01-CA-115296 (JVF), R21-CA- 110185 (JVF), and R33-EB-000673 (JVF and MGB), and an Application Development Award (JVF) from the Center for Integration of Medicine and Innovative Technology (CIMIT).

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Correspondence to John V. Frangioni MD, PhD.

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Tanaka, E., Choi, H.S., Fujii, H. et al. Image-Guided Oncologic Surgery Using Invisible Light: Completed Pre-Clinical Development for Sentinel Lymph Node Mapping. Ann Surg Oncol 13, 1671–1681 (2006). https://doi.org/10.1245/s10434-006-9194-6

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Keywords

  • Sentinel lymph node mapping
  • Pre-clinical development
  • Near-infrared light
  • Near-infrared fluorescence
  • Melanoma
  • Sinclair pigs