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

¹ Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
² Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
³ Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA

Correspondence: Address correspondence and reprint requests to: John V. Frangioni, MD, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, MA 02215, USA; E-mail: jfrangio{at}bidmc.harvard.edu

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.

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

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