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  • Title: γ-Glutamyltranspeptidase (GGT)-Activatable Fluorescence Probe for Durable Tumor Imaging.
    Author: Obara R, Kamiya M, Tanaka Y, Abe A, Kojima R, Kawaguchi T, Sugawara M, Takahashi A, Noda T, Urano Y.
    Journal: Angew Chem Int Ed Engl; 2021 Jan 25; 60(4):2125-2129. PubMed ID: 33096584.
    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-CH2 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.
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