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      Simultaneous Mapping of Pan and Sentinel Lymph Nodes for Real-Time Image-Guided Surgery

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          Abstract

          The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.

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          Technical details of intraoperative lymphatic mapping for early stage melanoma.

          D Morton, D Wen, J Wong … (1992)
          The initial route of metastases in most patients with melanoma is via the lymphatics to the regional nodes. However, routine lymphadenectomy for patients with clinical stage I melanoma remains controversial because most of these patients do not have nodal metastases, are unlikely to benefit from the operation, and may suffer troublesome postoperative edema of the limbs. A new procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases in 40 specimens (21%) on examination of routine hematoxylin-eosin-stained slides (12%) or exclusively in immunohistochemically stained preparations (9%). Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastasis in only two of 3079 nodes from 194 lymphadenectomy specimens that had an identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy.
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            The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery.

            Boudewijn Schaafsma, J. Mieog, Merlijn Hutteman … (2011)
            Optical imaging using near-infrared (NIR) fluorescence provides new prospects for general and oncologic surgery. ICG is currently utilised in NIR fluorescence cancer-related surgery for three indications: sentinel lymph node (SLN) mapping, intraoperative identification of solid tumours, and angiography during reconstructive surgery. Therefore, understanding its advantages and limitations is of significant importance. Although non-targeted and non-conjugatable, ICG appears to be laying the foundation for more widespread use of NIR fluorescence-guided surgery. Copyright © 2011 Wiley-Liss, Inc.
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              Rapid translocation of nanoparticles from the lung airspaces to the body.

              Edmond Choi, Akira Tsuda, S. H. Kim … (2010)
              Nano-size particles show promise for pulmonary drug delivery, yet their behavior after deposition in the lung remains poorly understood. In this study, a series of near-infrared (NIR) fluorescent nanoparticles were systematically varied in chemical composition, shape, size and surface charge, and their biodistribution and elimination were quantified in rat models after lung instillation. We demonstrate that nanoparticles with hydrodynamic diameter (HD) less than ≈34 nm and a noncationic surface charge translocate rapidly from the lung to mediastinal lymph nodes. Nanoparticles of HD < 6 nm can traffic rapidly from the lungs to lymph nodes and the bloodstream, and then be subsequently cleared by the kidneys. We discuss the importance of these findings for drug delivery, air pollution and carcinogenesis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Theranostics
                Journal ID (iso-abbrev): Theranostics
                Journal ID (publisher-id): thno
                Title: Theranostics
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1838-7640
                Publication date Collection: 2014
                Publication date (Electronic): 24 April 2014
                Volume: 4
                Issue: 7
                Pages: 693-700
                Affiliations
                1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
                2. Division of Cancer Diagnostics and Therapeutics, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
                3. Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
                4. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
                5. Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, South Korea
                Author notes
                ✉ Corresponding author: Hak Soo Choi, Ph.D. 330 Brookline Avenue, Room SL-436A, Boston, MA 02215. Tel: 617-667-6024, Fax: 617-975-5016; E-mail: hchoi@ 123456bidmc.harvard.edu .

                * These authors contributed equally to this work.

                Conflict of Interest: FLARE™ technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. It has been licensed to the FLARE Foundation, a non-profit organization focused on promoting the dissemination of medical imaging technology for research and clinical use. Dr. Frangioni is the founder and chairman of the FLARE Foundation. The Beth Israel Deaconess Medical Center will receive royalties for sale of FLARE™ Technology. Dr. Frangioni has elected to surrender post-market royalties to which he would otherwise be entitled as inventor, and has elected to donate pre-market proceeds to the FLARE Foundation. Dr. Frangioni has started three for-profit companies, Curadel, Curadel ResVet Imaging, and Curadel Surgical Innovations, which may someday be non-exclusive sub-licensees of FLARE™ technology.

                Article
                Publisher ID: thnov04p0693
                DOI: 10.7150/thno.8721
                PMC ID: 4038751
                PubMed ID: 24883119
                SO-VID: 8c589dd0-0ce5-4faa-92ec-f5e72ef6c211
                Copyright © © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                Date received : 30 January 2014
                Date accepted : 24 March 2014
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Molecular medicine
                Keywords: near-infrared fluorescence,pan lymph node mapping,completion lymphadenectomy,sentinel lymph node mapping,image-guided surgery,cervical cancer.
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: near-infrared fluorescence, pan lymph node mapping, completion lymphadenectomy, sentinel lymph node mapping, image-guided surgery, cervical cancer.

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