Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe.

Abstract

The ability of the unaided human eye to detect small cancer foci or accurate borders between cancer and normal tissue during surgery or endoscopy is limited. Fluorescent probes are useful for enhancing visualization of small tumors but are typically limited by either high background signal or the requirement for administration hours to days before use. We synthesized a rapidly activatable, cancer-selective fluorescence imaging probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), with intramolecular spirocyclic caging for complete quenching. Activation occurs by rapid one-step cleavage of glutamate with γ-glutamyltranspeptidase (GGT), which is not expressed in normal tissue, but is overexpressed on the cell membrane of various cancer cells, thus leading to complete uncaging and dequenching of the fluorescence probe. In vitro activation of gGlu-HMRG was evident in 11 human ovarian cancer cell lines tested. In vivo in mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRG occurred within 1 min of topically spraying the tumor, creating high signal contrast between the tumor and the background. The gGlu-HMRG probe is practical for clinical application during surgical or endoscopic procedures because of its rapid and strong activation upon contact with GGT on the surface of cancer cells.

• Authors: Yasuteru Urano, Masayo Sakabe, Nobuyuki Kosaka, Mikako Ogawa, Makoto Mitsunaga, Daisuke Asanuma, Mako Kamiya, Matthew R Young, Tetsuo Nagano, Peter L Choyke, Hisataka Kobayashi
• Journal: Science translational medicine (Sci Transl Med) Vol. 3 Issue 110 Pg. 110ra119 (Nov 23 2011) ISSN: 1946-6242 [Electronic] United States
• PMID: 22116934 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorescent Dyes
• Rhodamines
• gamma-Glutamyltransferase

Topics

• Administration, Topical
• Animals
• Cell Line, Tumor
• Early Detection of Cancer (methods)
• Female
• Fluorescent Dyes (administration & dosage, analysis)
• Humans
• Mice
• Neoplasms (diagnosis, pathology)
• Rhodamines (chemistry, metabolism)
• Sensitivity and Specificity
• Spectrometry, Fluorescence
• gamma-Glutamyltransferase (metabolism)