The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping

• Published in: Annals of surgical oncology Vol. 16; no. 10; pp. 2943 - 2952
• Main Authors: Troyan, Susan L., Kianzad, Vida, Gibbs-Strauss, Summer L., Gioux, Sylvain, Matsui, Aya, Oketokoun, Rafiou, Ngo, Long, Khamene, Ali, Azar, Fred, Frangioni, John V.
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.10.2009; Springer Nature B.V
• Subjects: Aged; Animals; Breast Neoplasms - diagnosis; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - surgery; Coloring Agents; Female; Fluorescence; Fluorometry - methods; Humans; Indocyanine Green; Intraoperative Period; Lymph Nodes - diagnostic imaging; Lymph Nodes - pathology; Lymphatic Metastasis; Medicine; Medicine & Public Health; Middle Aged; Oncology; Pilot Projects; Radionuclide Imaging; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Surgery; Surgery, Computer-Assisted; Surgical Oncology; Sus scrofa; Technetium Tc 99m Sulfur Colloid; Translational Research and Biomarkers; Sentinel Lymph Node; Methylene Blue; Human Serum Albumin; Flare; Sentinel Lymph Node Mapping
• ISSN: 1068-9265; 1534-4681; 1534-4681
• DOI: 10.1245/s10434-009-0594-2

Background Invisible NIR fluorescent light can provide high sensitivity, high-resolution, and real-time image-guidance during oncologic surgery, but imaging systems that are presently available do not display this invisible light in the context of surgical anatomy. The FLARE ™ imaging system overcomes this major obstacle. Methods Color video was acquired simultaneously, and in real-time, along with two independent channels of NIR fluorescence. Grayscale NIR fluorescence images were converted to visible “pseudo-colors” and overlaid onto the color video image. Yorkshire pigs weighing 35 kg (n = 5) were used for final preclinical validation of the imaging system. A six-patient pilot study was conducted in women undergoing sentinel lymph node (SLN) mapping for breast cancer. Subjects received 99m Tc-sulfur colloid lymphoscintigraphy. In addition, 12.5 μg of indocyanine green (ICG) diluted in human serum albumin (HSA) was used as an NIR fluorescent lymphatic tracer. Results The FLARE ™ system permitted facile positioning in the operating room. NIR light did not change the look of the surgical field. Simultaneous pan-lymphatic and SLN mapping was demonstrated in swine using clinically available NIR fluorophores and the dual NIR capabilities of the system. In the pilot clinical trial, a total of nine SLNs were identified by 99m Tc- lymphoscintigraphy and nine SLNs were identified by NIR fluorescence, although results differed in two patients. No adverse events were encountered. Conclusions We describe the successful clinical translation of a new NIR fluorescence imaging system for image-guided oncologic surgery.