Intraoperative Near-Infrared Fluorescence-Guided Peripheral Lung Tumor Localization in Rabbit Models
Intraoperative Near-Infrared Fluorescence-Guided Peripheral Lung Tumor Localization in Rabbit Models
复制标题
兔模型中术中近红外荧光引导周围肺肿瘤定位
DOI：
10.1016/j.athoracsur.2018.08.020
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Yasufuku Kazuhiro
中科院分区：
文献类型：
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作者：
Wada Hironobu;Zheng Jinzi;Gregor Alexander;Hirohashi Kentaro;Hu Hsin-Pei;Patel Priya;Ujiie Hideki;Kato Tatsuya;Anayama Takashi;Jaffray David A.;Yasufuku Kazuhiro
一种新型的脂质体纳米粒CF800，它共包裹了用于近红外成像的吲哚青绿和用于计算机断层成像的碘海醇，通过增强渗透性和滞留效应，显示了静脉注射后肿瘤的优先聚集。我们假设CF800增强的近红外成像有助于术中定位小的肺结节。CF800被静脉注射，随后进行连续CT扫描以跟踪CF800的生物分布。11只兔于开胸术后各时间点至注药后7d，用近红外荧光胸腔镜进行活体近红外荧光检测。取感兴趣器官进行近红外成像，进行体外分析。结果CT和近红外成像均显示CF800在VX2肿瘤内积聚增强。NIR图像分析显示第4天和第5天的肿瘤与背景的比率最高。第2天的高背景和第7天的低肿瘤信号阻止了明显的分界。肺转移瘤(直径小于2 mm)在第4天可被近红外成像成功显示。然而，近红外信号穿透有限，导致少数位于肺表面深处(<0 mm)的肿瘤定位失败。结论在一定条件下，近红外图像引导下的肺小结节定位是可行的。然而，需要进一步的细化以增加肿瘤信号强度并减少来自正常肺实质的背景信号，这至少在一定程度上是血管系统中持续的CF800的结果。
BackgroundA novel liposomal nanoparticle, CF800, that co-encapsulates indocyanine green for near-infrared (NIR) imaging and iohexol for computed tomography (CT) imaging has shown preferential tumor accumulation after intravenous injection by the enhanced permeability and retention effect. We hypothesized that CF800-enhanced NIR imaging would facilitate intraoperative localization of small lung nodules.MethodsA rabbit VX2 lung tumor model was implemented. CF800 was injected intravenously, followed by sequential CT acquisitions to track the biodistribution of CF800. Eleven rabbits were used for NIR fluorescence evaluation after thoracotomy at time points until 7 days after injection by using a NIR fluorescence thoracoscope in vivo. Organs of interests were removed for ex vivo analysis by using NIR imaging. Tumor-to-background (inflated lung) ratio was calculated and compared among the time points.ResultsBoth CT and NIR imaging indicated enhanced accumulation of CF800 within the VX2 tumor. NIR image analysis revealed the highest tumor-to-background ratio on days 4 and 5. High background at day 2 and low tumor signal at day 7 prevented distinct demarcation. Metastatic pulmonary small nodules (less than 2 mm in diameter) were successfully visualized by NIR imaging on day 4. However, NIR signal penetration was limited, resulting in localization failure for the few tumors deep (>0 mm) to the lung surface.ConclusionsNIR image-guided localization of small lung nodules appears to be feasible under certain conditions. However, further refinement will be required to increase tumor signal intensity and to reduce background signal from normal lung parenchyma, which is at least in part a consequence of persistent CF800 in the vasculature.