In vivo tumor imaging by a γ-glutamyl transpeptidase-activatable near-infrared fluorescent probe

gamma-Glutamyl transpeptidase (GGT), overexpressed in various cancer cells, has been perceived as a latent tumor biomarker. Thus, developing near-infrared (NIR) fluorescent GGT probes is highly desired for in vivo tumor imaging and studies. To our knowledge, however, such a GGT probe is still rare. Herein, we construct a new GGT-activatable NIR fluorescent probe HCAGlu by incorporating -glutamyl group as a recognition unit directly into a NIR hemicyanine fluorophore. HCAGlu exhibits a highly sensitive and selective NIR fluorescence off-on response to GGT. The probe has been applied to cell and histological section imaging, which demonstrates the ability of HCAGlu in distinguishing different GGT-expression levels in situ in biological samples. Notably, in vivo fluorescence imaging in tumor-bearing mice has been performed, verifying that probe HCAGlu can rapidly produce a distinct fluorescence signal in the tumor site via both intravenous and intratumoral injections. The simplicity and excellent performance of HCAGlu make it of high potential in studying the physiological function of GGT in vivo.