Surgical resection is widely used for tumor treatment, necessitating approaches for the precise locating of elusive tumor foci. We report the high performance detection of tumors in mice with fluorescein-isothiocyanate (FITC) labelled sialic acid (FITC-SA), a fluorescent monosaccharide with low cytoxicity. Analysis of mice intravenously injected with FITC-SA revealed high target-to-background fluorescence ratios in subcutaneous tumors and liver tumor implants with 0.2-5 mm diameters, which are significantly below the clinical threshold of minimal residual cancer (∼1 cm clearance). Extracellular FITC-SA is quickly cleared from circulation whereas the intracellular FITC-SA could be metabolically incorporated into glycoproteins via a cellular sialylation pathway. Compared with FITC-SA-laden nanoparticles, free FITC-SA is preferentially and quickly taken up by tumors in mice and displays high tumor-to-background signal contrast, suggesting the potential for fluorescence directed surgical ablation of tumors.
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