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6QC-ICG is a quenched fluorescent activity-based probe (qABP) developed by the Leiden University Medical Center (LUMC) for the intraoperative detection of breast cancer and ductal carcinoma in situ (DCIS). The probe is designed to target active cysteine cathepsins (specifically cathepsins B, L, and S), which are enzymes frequently overexpressed in the tumor microenvironment by both tumor cells and tumor-associated macrophages. 6QC-ICG consists of a targeting moiety that covalently binds to the active site of these enzymes and a fluorophore, Indocyanine Green (ICG), which is initially quenched. Upon covalent binding to the target enzyme, the quenching moiety is released, resulting in a "turn-on" fluorescent signal. This mechanism allows for high tumor-to-background ratios, enabling real-time visualization of tumor margins during breast-conserving surgery to potentially reduce the rate of incomplete resections.
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