Circulating tumor cells (CTCs) play an essential role in metastasis and serve as an important prognostic biomarker. The technology of CTC labeling and detection in vivo can greatly improve the research of cancer metastasis and therapy. However, there is no in vivo technology to detect CTCs in clinic. In this study, we demonstrate that 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG), a 2-deoxy-glucose analog, can work in vivo to indicate CTCs and metastases fluorescently by direct intravenous injection. During the development of an implanted tumor in mice, the spontaneous CTCs released from the primary tumor into blood vessels can be labeled by 2-NBDG due to the abnormal metabolism of CTCs. The green fluorescence of 2-NBDG from CTCs is then noninvasively detected by an in vivo flow cytometry system. Due to the high uptake of glucose by tumor cells, the CTCs in mice can maintain a high 2-NBDG level and thus be distinguished by 2-NBDG fluorescence in vivo efficiently, enabling tumor detection in vivo like positron emission tomography (PET) but at the single-cell resolution. Our results suggest 2-NBDG, a glucose analog with high biosafety, holds promising potential in clinical applications, similar to the widely-used contrast medium 2-F¹⁸-fluorodeoxyglucose in PET.

中文翻译：

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通过体内流式细胞术实时监测单个循环肿瘤细胞与荧光标记的脱氧葡萄糖

循环肿瘤细胞 (CTC) 在转移中起重要作用，并作为重要的预后生物标志物。体内CTC标记和检测技术可以极大地改善癌症转移和治疗的研究。然而，临床上还没有体内检测CTCs的技术。在本研究中，我们证明 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG)，一种 2-deoxy-glucose 类似物，可以在体内发挥作用，表明通过直接静脉注射荧光 CTCs 和转移。在小鼠植入肿瘤的发展过程中，由于 CTC 代谢异常，从原发肿瘤释放到血管中的自发 CTC 可以被 2-NBDG 标记。然后通过体内流式细胞术系统无创检测来自 CTC 的 2-NBDG 的绿色荧光。由于肿瘤细胞对葡萄糖的高摄取，小鼠体内的 CTC 可以维持高 2-NBDG 水平，从而在体内通过 2-NBDG 荧光有效区分，实现体内肿瘤检测，如正电子发射断层扫描 (PET)，但在单细胞分辨率。我们的结果表明 2-NBDG，一种具有高生物安全性的葡萄糖类似物，PET 中的^18-氟脱氧葡萄糖。