Image-guided oncologic surgery using invisible light: Completed pre-clinical development for sentinel lymph node mapping
Image-guided oncologic surgery using invisible light: Completed pre-clinical development for sentinel lymph node mapping
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DOI：
10.1245/s10434-006-9194-6
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发表时间：
2006-12-01
影响因子：
3.7
通讯作者：
Frangioni, John V.
中科院分区：
文献类型：
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作者：
Tanaka, Eiichi;Choi, Hak Soo;Frangioni, John V.
背景：不可见的近红外（NIR）荧光灯在肿瘤手术中提供高灵敏度、实时的图像引导，而不会改变手术视野的外观。在这项研究中，我们完成了使用大型自发性黑色素瘤动物模型进行前哨淋巴结（SLN）定位技术的临床前开发。方法：采用与人类黑色素瘤相似的自发性黑色素瘤转移到局部淋巴结的辛克莱猪。测试的有机淋巴示踪剂包括fda批准的非共价吸附于人血清白蛋白（HSA）的吲哚菁绿，以及共价结合于人血清白蛋白（HSA800）的近红外荧光团CW800。测试的无机/有机杂化示踪剂是带阴离子涂层的II型近红外量子点。原发肿瘤接受四次肿瘤周围注射每种示踪剂，每次注射荧光团剂量为100 pmol至1 nmol。实时进行SLN定位和图像引导切除。结果：3种淋巴示踪剂分别注射到6只动物的n = 4个单独的原发性黑色素瘤中。所有12次注射均在100%的病例中在1分钟内识别出SLN(s)及其相关淋巴通道，尽管皮肤色素沉着，皮毛黑色。水动力直径对示踪剂在体内的行为有深远的影响。结论：本研究完成了近红外荧光引导SLN定位的临床前开发，为未来的人体临床试验提供了成像系统优化和示踪剂选择的见解。该技术可能会消除对放射性和彩色示踪剂的需求，在整个过程中允许实时图像引导，并协助病理学家进行组织分析。
Background: Invisible near-infrared (NIR) fluorescent light permits high sensitivity, real-time image-guidance during oncologic surgery without changing the look of the surgical field. In this study, we complete pre-clinical development of the technology for sentinel lymph node (SLN) mapping using a large animal model of spontaneous melanoma.Methods: Sinclair swine with spontaneous melanoma metastatic to regional lymph nodes were used because of their similarity to human melanoma. Organic lymphatic tracers tested included FDA-approved indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic hybrid tracer tested was type II NIR quantum dots with an anionic coating. Primary tumors received four peri-tumoral injections of each tracer, with a fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image-guided resection were performed in real-time.Results: Each of the 3 lymphatic tracers was injected into n = 4 separate primary melanomas in a total of 6 animals. All 12 injections resulted in identification of the SLN(s) and their associated lymphatic channels within 1 minute in 100% of cases, despite highly pigmented skin and black fur. Hydrodynamic diameter had a profound impact on tracer behavior in vivo.Conclusion: This study completes the pre-clinical development of NIR fluorescence-guided SLN mapping and provides insight into imaging system optimization and tracer choice for future human clinical trials. The technology is likely to eliminate the need for radioactive and colored tracers, permits real-time image guidance throughout the procedure, and assists the pathologist in tissue analysis.