Real-time monitoring of single circulating tumor cells with a fluorescently labeled deoxy-glucose by in vivo flow cytometry.

Abstract

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.