Combination of an Integrin-Targeting NIR Tracer and an Ultrasensitive Spectroscopic Device for Intraoperative Detection of Head and Neck Tumor Margins and Metastatic Lymph Nodes.
Combination of an Integrin-Targeting NIR Tracer and an Ultrasensitive Spectroscopic Device for Intraoperative Detection of Head and Neck Tumor Margins and Metastatic Lymph Nodes.
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DOI：
10.18383/j.tom.2016.00253
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Shim H
中科院分区：
文献类型：
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作者：
Yoon Y;Mohs AM;Mancini MC;Nie S;Shim H
尽管靶向药物治疗和放射治疗取得了重大进展，但手术仍然是大多数实体瘤最有效的治疗方法。患者生存的最重要的预测因素是原发肿瘤、引流淋巴结和转移病灶的完整手术切除。然而，目前接受手术的头颈癌患者仍有20%~30%因漏诊病灶而未能完全切除而离开手术室。因此，存在开发先进成像示踪剂和术中仪器的重大机会，使外科医生能够在手术期间可视化微观肿瘤。细胞粘附分子整合素αvβ3由肿瘤新生血管和侵入的肿瘤细胞特异性表达，但不由静止血管或正常细胞表达。在这里，我们报告了整合素靶向近红外示踪剂（RGD-IRDye800CW）和手持式光谱设备（具有宽视野成像系统的集成点光谱仪）的组合使用，用于高灵敏度检测浸润癌细胞上的整合素过度表达。通过使用原位头颈癌动物模型，我们表明这种示踪剂-设备组合不仅可以在术中检测浸润性肿瘤边缘，还可以检测转移性淋巴结。相关组织学分析进一步揭示，术中可检测到50-100个肿瘤细胞的微小簇，具有高灵敏度和特异性，为指导手术切除微小肿瘤和转移淋巴结提供了新的可能性。
Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%–30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. Here we report the combined use of an integrin-targeting near-infrared tracer (RGD-IRDye800CW) and a handheld spectroscopic device, an integrated point spectroscopy with wide-field imaging system, for highly sensitive detection of integrin overexpression on infiltrating cancer cells. By using an orthotopic head and neck cancer animal model, we show that this tracer–device combination allows intraoperative detection of not only invasive tumor margins but also metastatic lymph nodes. Correlated histological analysis further reveals that microscopic clusters of 50–100 tumor cells can be detected intraoperatively with high sensitivity and specificity, raising new possibilities in guiding surgical resection of microscopic tumors and metastatic lymph nodes.