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Gan to kagaku ryoho. Cancer & chemotherapy

[In vivo cancer detection with a newly designed fluorescent probe].


PMID 23507591

Abstract

Fluorescence imaging is one of the most powerful techniques currently available for continuous observation of dynamic intracellular processes in living cells. Suitable fluorescence probes are naturally of critical importance for fluorescence imaging, and we have succeeded to construct several versatile rational design strategies for novel fluorescence probes based on the concept of photoinduced electron transfer and intramolecular spirocyclization. Very recently, we have succeeded to develop various novel protease probes which were applicable for living cell system. For example, gGlu-HMRG, a novel spirocyclized rhodamine-based fluorescence probe for γ-glutamyltranspeptidase(GGT), which is well-known to be upregulated in various cancer cells, was successfully developed. By applying gGlu-HMRG to various cancerous cell lines whose GGT activity is upregulated, fast enzymatic reaction of gGlu-HMRG with GGT occurs on the plasma membrane to yield highly fluorescent product HMRG, which led us to establish a novel and highly activatable strategy for sensitive and fast-responding fluorescence imaging of tiny tumors in vivo. In mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRG occurred within 1 min of topically spraying onto tissue surfaces that are suspected of harboring tumors, creating high signal contrast between the tumor and the background. We believe gGlu-HMRG probe could aid surgeons in detecting tiny cancerous nodules for accurate biopsy and tumor resection, delineating the borders of tumors for complete removal and confirming no residual tumor.