Small Molecules for Multi-Wavelength Near-Infrared Fluorescent Mapping of Regional and Sentinel Lymph Nodes in Colorectal Cancer Staging
| Autor: | Anton G. T. Terwisscha van Scheltinga, Cornelis F. M. Sier, Victor M Baart, Shadhvi S. Bhairosingh, Taryn L. March, John V. Frangioni, Maged Henary, Marion M. Deken, Peter J. K. Kuppen, Hoon Hyun, Mark W. Bordo, Hak Soo Choi, Alexander L. Vahrmeijer, Daniela C.F. Salvatori, Adrianus R. P. M. Valentijn |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research indocyanine green image-guided surgery Colorectal cancer Sentinel lymph node Multi wavelength lcsh:RC254-282 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Lymph node Original Research Cancer staging business.industry cancer staging lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Fluorescence 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis ZW800 fluorescence Lymph Nuclear medicine business Indocyanine green |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, 10. FRONTIERS MEDIA SA Frontiers in Oncology, Vol 10 (2020) |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2020.586112 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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