Glycan Metabolic Fluorine Labeling for In Vivo Visualization of Tumor Cells and In Situ Assessment of Glycosylation Variations

The abnormality in the glycosylation of surface proteins is critical for the growth and metastasis of tumors and their capacity for immunosuppression and drug resistance. This anomaly offers an entry point for real‐time analysis on glycosylation fluctuations. In this study, we report a strategy, glycan metabolic fluorine labeling (MEFLA), for selectively tagging glycans of tumor cells. As a proof of concept, we synthesized two fluorinated unnatural monosaccharides with distinctive 19F chemical shifts (Ac4ManNTfe and Ac4GalNTfa). These two probes could undergo selective uptake by tumor cells and subsequent incorporation into surface glycans. This approach enables efficient and specific 19F labeling of tumor cells, which permits in vivo tracking of tumor cells and in situ assessment of glycosylation changes by 19F MRI. The efficiency and specificity of our probes for labeling tumor cells were verified in vitro with A549 cells. The feasibility of our method was further validated with in vivo experiments on A549 tumor‐bearing mice. Moreover, the capacity of our approach for assessing glycosylation changes of tumor cells was illustrated both in vitro and in vivo. Our studies provide a promising means for visualizing tumor cells in vivo and assessing their glycosylation variations in situ through targeted multiplexed 19F MRI. We developed a strategy called glycan MEtabolic Fluorine LAbeling (glycan MEFLA) for selectively tagging glycans of tumor cells. It allows for efficient and selective labeling of tumor cells by fluorinated monosaccharide‐based probes (Ac4ManNTfe and Ac4GalNTfa), enabling in vivo visualization of tumor cells and in situ assessment of glycosylation changes via 19F MRI with high sensitivity and deep penetration.