Open AccessNear-infrared fluorescence lymphatic imaging in vascular endothelial growth factor-C overexpressing murine melanoma
Author(s) -
Sunkuk Kwon,
Fred Christian Velasquez,
Eva M. SevickMuraca
Publication year - 2018
Publication title -
biomedical optics express
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.362
H-Index - 86
ISSN - 2156-7085
DOI - 10.1364/boe.9.004631
Subject(s) - lymphatic system , pathology , lymphatic vessel , extravasation , melanoma , evans blue , medicine , lymphatic endothelium , vascular endothelial growth factor c , vascular endothelial growth factor , vascular permeability , lymph , vegf receptors , cancer research , vascular endothelial growth factor a , cancer , metastasis
In this study we employ a near-infrared fluorescence lymphatic imaging (NIRFLI) technique to longitudinally image spatial and temporal changes in the lymphatics in mice bearing vascular endothelial growth factor (VEGF)-C overexpressing B16F10 (VEGF-C-B16F10) or mock-transduced B16F10 (mock-B16F10) melanoma tumors. Our NIRFLI data show that ICG-laden lymph accumulates into a VEGF-C-B16F10 tumor compared to mock-B16F10 at 3 days post implantation, presumably due to increased lymphatic vessel permeability. Quantification shows a significantly greater percentage of ICG-perfused area in VEGF-C-B16F10 (7.6 ± 2) as compared to MOCK-B16F10 (1 ± 0.5; p = 0.02), which is also confirmed by quantification of the lymphatic leakage of evans blue dye (optical density at 610nm; VEGF-C-B16F10, 10.5 ± 2; mock-B16F10, 5.1 ± 0.5; p = 0.009); thereafter, lymphatic leakage is visualized only in the peritumoral region. Our imaging data also show that anti-VEGF-C treatment in VEGF-C-B16F10 restores normal lymphatic vessel integrity and reduces dye extravasation. Because NIRFLI technology can be used to non-invasively detect lymphatic changes associated with cancer, it may provide a new diagnostic to assess the lack of lymphatic vessel integrity that promotes lymphovascular invasion and to assess therapies that could arrest invasion through normalization of the lymphatic vasculature.