The standard of care in breast cancer surgery includes identification and assessment of the sentinel lymph node (SLN). At the present time, SLN mapping utilizes a gamma ray-emitting radiotracer and/or a blue dye. Radiotracers provide sensitive detection of SLNs, but require involvement of a nuclear medicine physician, vary widely in transit time depending on the agent employed, can be difficult to localize with a handheld gamma probe, and expose both patient and caregivers to ionizing radiation. Blue dyes, such as isosulfan blue, cannot be seen easily through skin and fat, but can aid in definitive identification of the SLN when the handheld gamma probe gives ambiguous results. Finally, the learning curve associated with expertise in the SLN procedure is quite long using currently available techniques. In this application, we describe an optical imaging technology that enables the surgeon to follow lymphatic flow in real-time from the injection site to the SLN, and to resect the SLN under sensitive image- guidance. As part of an NIH-funded Bioengineering Research Partnership, our laboratory has already developed a near-infrared (NIR) fluorescence imaging system that uses harmless, invisible NIR light, makes no contact with the patient, and has no moving parts. Surgical anatomy is displayed in color simultaneously with an overlay of NIR fluorescence to assess the surgical field objectively. Our laboratory also has considerable experience with the chemistry of NIR fluorophores and has developed a simple formulation (ICG:HSA) of FDA- approved indocyanine green (ICG) adsorbed non-covalently to human serum albumin (HSA) that results in a three-fold increase in quantum yield, and adequate retention in the SLN. Using large animal model systems, some with spontaneous tumors metastatic to regional lymph nodes, we have validated NIR fluorescent SLN mapping in the skin, mammary tissue, esophagus, stomach, colon, lung, pleural space, and peritoneal space. Our studies suggest that the technology is now ready for clinical translation. In this clinical study we will collaborate with Susan L. Troyan, M.D., an academic breast cancer surgeon who performs more than 100 SLN mapping procedures annually at our institution. All patients will receive the standard of care using filtered 99mTc-sulfur colloid.
In Specific Aim 1, we propose a blinded Phase I safety study of the imaging system in combination with ICG:HSA;
this Specific Aim will determine optimal dose, light excitation fluence rate, and camera exposure time.
In Specific Aim 2, we propose a Phase II study during which ICG:HSA will be used to guide SLN identification and resection, and 99mTc-sulfur colloid will be used to confirm the SLN. This study will define the advantages and limitations of NIR fluorescent SLN mapping for breast cancer. If proven successful, the technology could potentially improve patient care by eliminating the need for ionizing radiation and blue dye, shortening the learning curve, and reducing the length of the procedure.7. PROJECT NARRATIVE: Sentinel lymph node (SLN) mapping is the standard of care for the surgical staging of breast cancer. We propose a method of SLN mapping based on the use of invisible near-infrared fluorescent light that has significant advantages for both patient and surgeon.
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