Near-infrared fluorescence lymphatic imaging in vascular endothelial growth factor-C overexpressing murine melanoma.
Near-infrared fluorescence lymphatic imaging in vascular endothelial growth factor-C overexpressing murine melanoma.
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DOI：
10.1364/boe.9.004631
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发表时间：
2018-09
影响因子：
3.4
通讯作者：
Sunkuk Kwon;F. C. Velasquez;E. Sevick-Muraca
中科院分区：
文献类型：
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作者：
Sunkuk Kwon;F. C. Velasquez;E. Sevick-Muraca
在这项研究中，我们使用近红外荧光淋巴成像(NIRFLI)技术纵向成像血管内皮生长因子(VEGF)-C过表达B16F10(VEGF-C-B16F10)或模拟转导B16F10(模拟B16F10)黑色素瘤小鼠淋巴管的时空变化。我们的NIRFLI数据显示，与模型B16F10相比，植入后3天，携带ICG的淋巴聚集到VEGF-C-B16F10肿瘤中，可能是由于淋巴管通透性增加所致。定量显示血管内皮生长因子C-B16F10的ICG灌注区百分比(7.6±2)明显高于模型B16F10(1±0.5；p=0.02)，伊文思蓝的淋巴渗漏定量也证实了这一点(光密度610 nm；血管内皮生长因子-C-B16F10，10.5±2；模型B16F10，5.1±0.5；p=0.009)；我们的成像数据还显示，在血管内皮生长因子-C-B16F10中进行抗血管内皮生长因子-C治疗可以恢复正常淋巴管的完整性，减少染料渗出。由于NIRFLI技术可用于非侵入性地检测与癌症相关的淋巴管变化，它可能提供一种新的诊断方法，以评估促进淋巴管侵袭的淋巴管完整性的缺乏，并评估通过淋巴管系统正常化来阻止侵袭的治疗方法。
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.