Small Molecules for Multi-Wavelength Near-Infrared Fluorescent Mapping of Regional and Sentinel Lymph Nodes in Colorectal Cancer Staging

Assessing lymph node (LN) status during tumor resection is fundamental for the staging of colorectal cancer. Current guidelines require a minimum of 12 LNs to be harvested during resection and ultra-staging regional lymph nodes by sentinel lymph node (SLN) assessment is being extensively investigated. The current study presents novel near-infrared (NIR) fluorescent dyes for simultaneous pan lymph node (PanLN; regional) and SLN mapping. PanLN-Forte was intravenously injected in mice and assessed for accumulation in regional LNs. SLN800 was injected intradermally in mice, after which the collection and retention of fluorescence in SLNs were measured using indocyanine green (ICG) and its precursor, SLN700, as references. LNs in the cervical, inguinal, jejunal, iliac, and thoracic basins could clearly be distinguished after a low dose intravenous injection of PanLN-Forte. Background fluorescence was significantly lower compared to the parent compound ZW800-3A (p < 0.001). SLN700 and SLN800 specifically targeted SLNs with fluorescence being retained over 40-fold longer than the current clinically used agent ICG. Using SLN700 and SLN800, absolute fluorescence in SLN was at least 10 times higher than ICG in second-tier nodes, even at 1 hour post-injection. Histologically, the fluorescent signal localized in the LN medulla (PanLN-Forte) or sinus entry (SLN700/SLN800). PanLN-Forte and SLN800 appear to be optimal for real-time NIR fluorescence imaging of regional and SLNs, respectively.

[1]  Kevin W. Eliceiri,et al.  ImageJ for the Next Generation of Scientific Image Data , 2019, Microscopy and Microanalysis.

[2]  Alexander L Vahrmeijer,et al.  A zwitterionic near-infrared fluorophore for real-time ureter identification during laparoscopic abdominopelvic surgery , 2019, Nature Communications.

[3]  Pieterjan Debie,et al.  Latest developments in molecular tracers for fluorescence image-guided cancer surgery. , 2019, The Lancet. Oncology.

[4]  G. Choi,et al.  Clinical Implications of Lymph Node Metastasis in Colorectal Cancer: Current Status and Future Perspectives , 2019, Annals of coloproctology.

[5]  M. Carlucci,et al.  Clinicopathological Factors Influencing Lymph Node Yield in Colorectal Cancer: A Retrospective Study , 2019, Gastroenterology research and practice.

[6]  Jouke Dijkstra,et al.  A practical guide for the use of indocyanine green and methylene blue in fluorescence‐guided abdominal surgery , 2018, Journal of surgical oncology.

[7]  K. Hanazaki,et al.  Factors influencing the number of retrieved lymph nodes after colorectal resection: a retrospective study from a single institute. , 2018, International journal of clinical and experimental pathology.

[8]  Leonora S F Boogerd,et al.  Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study. , 2018, The lancet. Gastroenterology & hepatology.

[9]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[10]  Kevin W. Eliceiri,et al.  ImageJ2: ImageJ for the next generation of scientific image data , 2017, BMC Bioinformatics.

[11]  J. Putnam,et al.  Rationale for a Minimum Number of Lymph Nodes Removed with Non-Small Cell Lung Cancer Resection: Correlating the Number of Nodes Removed with Survival in 98,970 Patients , 2016, Annals of Surgical Oncology.

[12]  Chao Lu,et al.  Retrospective study , 2016, Medicine.

[13]  J. DeSimone,et al.  Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[14]  Shery Jacob,et al.  A simple practice guide for dose conversion between animals and human , 2016, Journal of basic and clinical pharmacy.

[15]  V. Lemmens,et al.  No change in lymph node positivity rate despite increased lymph node yield and improved survival in colon cancer. , 2014, European journal of cancer.

[16]  A. Purushotham,et al.  Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. , 2014, The Lancet. Oncology.

[17]  Hak Soo Choi,et al.  Simultaneous Mapping of Pan and Sentinel Lymph Nodes for Real-Time Image-Guided Surgery , 2014, Theranostics.

[18]  M. Raspa,et al.  FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units , 2014, Laboratory animals.

[19]  Y. Darwis,et al.  Advanced drug delivery to the lymphatic system: lipid-based nanoformulations , 2013, International journal of nanomedicine.

[20]  Cornelis J H van de Velde,et al.  Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer. , 2012, Gynecologic oncology.

[21]  R. Labianca,et al.  ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[22]  A. Cardona,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[23]  C. Buskens,et al.  Systematic Review of Sentinel Lymph Node Mapping Procedure in Colorectal Cancer , 2012, Annals of Surgical Oncology.

[24]  A. Renehan,et al.  Lymph node harvest in colon and rectal cancer: Current considerations. , 2012, World journal of gastrointestinal surgery.

[25]  J. Begun,et al.  Association between lymph node evaluation for colon cancer and node positivity over the past 20 years. , 2011, JAMA.

[26]  Merlijn Hutteman,et al.  The clinical use of indocyanine green as a near‐infrared fluorescent contrast agent for image‐guided oncologic surgery , 2011, Journal of surgical oncology.

[27]  Hak Soo Choi,et al.  Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. , 2011, Angewandte Chemie.

[28]  Cornelis J H van de Velde,et al.  Optimization of Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Cervical Cancer Patients , 2011, International Journal of Gynecologic Cancer.

[29]  Hein Putter,et al.  Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients , 2011, Breast Cancer Research and Treatment.

[30]  Sylvain Gioux,et al.  Toward Optimization of Imaging System and Lymphatic Tracer for Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Breast Cancer , 2011, Annals of Surgical Oncology.

[31]  Hak Soo Choi,et al.  Clinical Translation of Ex Vivo Sentinel Lymph Node Mapping for Colorectal Cancer Using Invisible Near-Infrared Fluorescence Light , 2010, Annals of Surgical Oncology.

[32]  J. Frangioni,et al.  Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation , 2010, Molecular imaging.

[33]  E. Sevick-Muraca,et al.  Functional lymphatic imaging in tumor-bearing mice. , 2010, Journal of immunological methods.

[34]  S. Scabini.  Sentinel node biopsy in colorectal cancer: Must we believe it? , 2010, World journal of gastrointestinal surgery.

[35]  Susan Newbigging,et al.  In vivo quantum-dot toxicity assessment. , 2010, Small.

[36]  J. Frangioni,et al.  Image-guided sentinel lymph node mapping and nanotechnology-based nodal treatment in lung cancer using invisible near-infrared fluorescent light. , 2009, Seminars in thoracic and cardiovascular surgery.

[37]  M. Choti,et al.  NCCN Clinical Practice Guidelines in Oncology: colon cancer. , 2009, Journal of the National Comprehensive Cancer Network : JNCCN.

[38]  Tristan Barrett,et al.  Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. , 2007, Nano letters.

[39]  W. Van den Broeck,et al.  Anatomy and nomenclature of murine lymph nodes: Descriptive study and nomenclatory standardization in BALB/cAnNCrl mice. , 2006, Journal of immunological methods.

[40]  M. Šimunović,et al.  Lymph node counts, rates of positive lymph nodes, and patient survival for colon cancer surgery in Ontario, Canada: A population‐based study , 2006, Journal of surgical oncology.

[41]  John V. Frangioni,et al.  Organic Alternatives to Quantum Dots for Intraoperative Near-Infrared Fluorescent Sentinel Lymph Node Mapping , 2005, Molecular imaging.

[42]  S. Gallinger,et al.  Lymph Node Retrieval and Assessment in Stage II Colorectal Cancer: A Population-Based Study , 2003, Annals of Surgical Oncology.

[43]  Yong Taik Lim,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular imaging.

[44]  S. Leeder,et al.  A population based study , 1993, The Medical journal of Australia.

[45]  María Blanca Fernández-Viñéa.  CURRENT STATUS AND FUTURE PERSPECTIVES , 2018 .

[46]  M. Bawendi,et al.  Sentinel lymph node mapping with type-II quantum dots. , 2007, Methods in molecular biology.

[47]  N. Petrelli,et al.  Clinical significance of colorectal cancer: Metastases in lymph nodes <5 mm in size , 2006, Annals of Surgical Oncology.

[48]  Ralph Weissleder,et al.  Pan and sentinel lymph node visualization using a near-infrared fluorescent probe. , 2003, Molecular imaging.

[49]  A. Maggi,et al.  [Colon Cancer]. , 1958, El Dia medico.