Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model.
Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model.
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作者：
Keating JJ;Runge JJ;Singhal S;Nims S;Venegas O;Durham AC;Swain G;Nie S;Low PS;Holt DE
肿瘤完全切除是非小细胞肺癌患者生存的最重要预测因素。肺癌切除术后的术中切缘评估方法缺乏。我们评估了近红外术中成像使用叶酸靶向分子造影剂（OTL 0038）定位原发性肺腺癌，淋巴结取样，边缘评估。10只患有肺癌的狗在静脉内注射OTL 0038后进行了电视辅助胸腔镜手术（VATS）或开胸手术和肿瘤切除。使用NIR成像装置在体内和离体对肺进行成像。对伤口床进行重新成像，以确定疑似阳性肿瘤边缘的残留荧光。所有病例均测量肿瘤信号背景比（SBR）。接下来，三名人类患者参加了一项原理验证研究。原位和离体测量肿瘤荧光。所有犬肿瘤均在原位发荧光（Fluoptics平均SBR 5.2（范围2.7-8.1）; Karl Storz平均SBR 2.9（范围1.4-2.6））。此外，荧光与病理学上的肿瘤边缘一致。使用NIR成像发现三个阳性淋巴结。此外，在伤口床的NIR成像中发现了阳性残留肿瘤边缘。人肺腺癌在原位和离体也是荧光的（平均SBR > 2.0）。NIR成像在大型动物模型中识别肺癌。此外，NIR成像可以区分携带癌细胞的淋巴结，并引起对阳性肿瘤边缘的注意。在人类中，肺腺癌在注射靶向造影剂后发出荧光。
Complete tumor resection is the most important predictor of patient survival from non-small cell lung cancer. Methods of intraoperative margin assessment following lung cancer excision are lacking. We evaluated near-infrared intraoperative imaging using a folate-targeted molecular contrast agent (OTL0038) for localization of primary lung adenocarcinoma, lymph node sampling, and margin assessment. Ten dogs with lung cancer underwent either video-assisted thoracoscopic surgery (VATS) or open thoracotomy and tumor excision following intravenous injection OTL0038. Lungs were imaged using a NIR imaging device both in vivo and ex vivo. The wound bed was re-imaged for retained fluorescence suspicious for positive tumor margins. Tumor signal-to-background ratio (SBR) was measured in all cases. Next, three human patients were enrolled in a proof-of-principle study. Tumor fluorescence was measured both in situ and ex vivo. All canine tumors fluoresced in situ (Fluoptics mean SBR 5.2 (range 2.7-8.1); Karl Storz mean SBR 2.9 (range 1.4-2.6). Additionally, fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered using NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR > 2.0). NIR imaging identifies lung cancer in a large animal model. Additionally, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after injecting the targeted contrast agent.