Intraoperative imaging of hepatic cancers using γ-glutamyltranspeptidase-specific fluorophore enabling real-time identification and estimation of recurrence

γ-Glutamyltranspeptidase (GGT) is upregulated in a variety of human cancers including primary and secondary hepatic tumors. This motivated us to use γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a novel fluorophore emitting light at around 520 nm following enzymatic reaction with GGT, as a tool for the intraoperative identification of hepatic tumors. gGlu-HMRG was topically applied to 103 freshly resected hepatic specimens. Fluorescence imaging using gGlu-HMRG identified hepatic tumors with the sensitivity/specificity of 48%/96% for hepatocellular carcinoma, 100%/100% for intrahepatic cholangiocarcinoma, and 87%/100% for colorectal liver metastasis. High gGlu-HMRG fluorescence intensity was positively associated with the incidence of microscopic vascular invasion in HCC and the risk of early postoperative recurrence in CRLM. These results suggest that gGlu-HMRG imaging could not only be a useful intraoperative navigation tool but also provide information related to postoperative disease recurrence.