Wang Yu, Lang Lixin, Huang Peng, Wang Zhe, Jacobson Orit, Kiesewetter Dale O, Ali Iqbal U, Teng Gaojun, Niu Gang, Chen Xiaoyuan
Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China; and Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):208-13. doi: 10.1073/pnas.1414821112. Epub 2014 Dec 22.
The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid)-conjugated truncated Evans blue ((18)F-AlF-NEB) and Evans blue (EB) dye. After local injection, both (18)F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from (18)F-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of (18)F-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance.
利用非侵入性成像方法准确且轻松地定位前哨淋巴结（SLN）的能力将有助于肿瘤分期和患者管理。为此，我们通过将氟 - 18 氟化铝标记的 NOTA（1,4,7 - 三氮杂环壬烷 - N，N'，N'' - 三乙酸）共轭截短伊文思蓝（¹⁸F - AlF - NEB）与伊文思蓝（EB）染料混合，开发了一种淋巴成像剂。局部注射后，¹⁸F - AlF - NEB 和 EB 均与组织间液中的内源性白蛋白形成复合物，从而实现淋巴系统的可视化。在三种不同的动物模型中进行了前哨淋巴结的正电子发射断层扫描（PET）和/或光学成像，包括后肢炎症模型、原位乳腺癌模型和转移性乳腺癌模型。在所有这三种模型中，前哨淋巴结均可通过伊文思蓝明显的蓝色和强荧光信号以及¹⁸F - AlF - NEB 的高强度 PET 信号清晰区分。前哨淋巴结之间的淋巴管也可通过光学方式可视化。其制备简便、PET 和光学成像质量优异以及生物安全性表明，¹⁸F - AlF - NEB 和 EB 的这种组合在临床应用中具有巨大潜力，可用于绘制前哨淋巴结图谱并提供术中指导。
