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MR and optical imaging of early micrometastases in lymph nodes: triple labeling with nano-sized agents yielding distinct signals.
Contrast Media & Molecular Imaging Pub Date : 2012-03-22 , DOI: 10.1002/cmmi.489
Nobuyuki Kosaka 1 , Marcelino Bernardo , Makoto Mitsunaga , Peter L Choyke , Hisataka Kobayashi
Affiliation  

Few imaging methods are available for depicting in vivo cancer cell migration within the lymphatic system. Detection of such early micrometastases requires extremely high target to background. In this study, we dual-labeled human breast cancer cells (MDA-MB468) with a small particle of iron oxide (SPIO) and a quantum dot (QD), and tracked these cells in the lymphatic system in mice using in vivo MRI and optical imaging. A generation-6 gadolinium-dendrimer-based MRI contrast agent (Gd-G6) was employed for visualizing regional lymphatic channels and nodes. Since Gd-G6 shortened T(1) leading to high signal, whereas SPIO-labeled cancer cells greatly lowered signal, a small number of cells were simultaneously visualized within the draining lymphatic basins. One million dual-labeled cancer cells were subcutaneously injected into the paws of mice 24 h prior to imaging. Then whole body images were acquired pre- and post-intracutaneous injection of Gd-G6 with 3D-T(1) w-FFE and balanced-FFE sequences for cancer cell tracking and MR lymphangiography. In vivo MRI clearly visualized labeled cancer cells migrating from the paw to the axillary lymph nodes using draining lymphatics. In vivo optical imaging using a fluorescence surgical microscope demonstrated tiny cancer cell clusters in the axillary lymph node with high spatial resolution. Thus, using a combination of MRI and optical imaging, it is possible to depict macro- and early micrometastases within the lymphatic system. This platform offers a versatile research tool for investigating and treating lymphatic metastases in animal models.

中文翻译:

淋巴结早期微转移的 MR 和光学成像:用纳米级药物进行三重标记,产生不同的信号。

很少有成像方法可用于描绘淋巴系统内的体内癌细胞迁移。这种早期微转移的检测需要极高的背景目标。在这项研究中,我们用小颗粒氧化铁 (SPIO) 和量子点 (QD) 对人乳腺癌细胞 (MDA-MB468) 进行双重标记,并使用 体内 MRI 和光学成像。第六代钆树枝状聚合物 MRI 造影剂 (Gd-G6) 用于可视化区域淋巴管和淋巴结。由于 Gd-G6 缩短了导致高信号的 T(1),而 SPIO 标记的癌细胞大大降低了信号,因此在引流淋巴盆内同时观察到少量细胞。在成像前 24 小时,将 100 万个双标记的癌细胞皮下注射到小鼠的爪子中。然后在皮内注射 Gd-G6 和 3D-T(1) w-FFE 和平衡 FFE 序列之前和之后获取全身图像,用于癌细胞跟踪和 MR 淋巴管造影。体内 MRI 清楚地显示了标记的癌细胞使用引流淋巴管从爪子迁移到腋窝淋巴结。使用荧光手术显微镜的体内光学成像显示腋窝淋巴结中具有高空间分辨率的微小癌细胞簇。因此,结合使用 MRI 和光学成像,可以描绘淋巴系统内的宏观和早期微转移。该平台提供了一种多功能的研究工具,用于研究和治疗动物模型中的淋巴转移。然后在皮内注射 Gd-G6 和 3D-T(1) w-FFE 和平衡 FFE 序列之前和之后获取全身图像,用于癌细胞跟踪和 MR 淋巴管造影。体内 MRI 清楚地显示了标记的癌细胞使用引流淋巴管从爪子迁移到腋窝淋巴结。使用荧光手术显微镜的体内光学成像显示腋窝淋巴结中具有高空间分辨率的微小癌细胞簇。因此,结合使用 MRI 和光学成像,可以描绘淋巴系统内的宏观和早期微转移。该平台提供了一种多功能的研究工具,用于研究和治疗动物模型中的淋巴转移。然后在皮内注射 Gd-G6 和 3D-T(1) w-FFE 和平衡 FFE 序列之前和之后获取全身图像,用于癌细胞跟踪和 MR 淋巴管造影。体内 MRI 清楚地显示了标记的癌细胞使用引流淋巴管从爪子迁移到腋窝淋巴结。使用荧光手术显微镜的体内光学成像显示腋窝淋巴结中具有高空间分辨率的微小癌细胞簇。因此,结合使用 MRI 和光学成像,可以描绘淋巴系统内的宏观和早期微转移。该平台提供了一种多功能的研究工具,用于研究和治疗动物模型中的淋巴转移。
更新日期:2019-11-01
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