γ‐Glutamyltranspeptidase (GGT)‐Activatable Fluorescence Probe for Durable Tumor Imaging

Abstract γ‐Glutamyltranspeptidase (GGT) is overexpressed in several types of cancer. Existing GGT‐targeting fluorescence probes can image these cancers, but the fluorescent hydrolysis product leaks from the target cancer cells during prolonged incubation or fixation. Here, we present a functionalized fluorescence probe for GGT, 4‐CH 2 F‐HMDiEtR‐gGlu, which is designed to generate an azaquinone methide intermediate during activation by GGT; this intermediate reacts with intracellular nucleophiles to generate a fluorescent adduct that is trapped inside the cells, without loss of the target enzyme activity. Application of the probe to patient‐derived xenograft (PDX) mice enabled in vivo cancer imaging for a prolonged period and was also compatible with fixation and immunostaining of the cancer tissue.