Research ArticleCancer Imaging

Rapid Cancer Detection by Topically Spraying a γ-Glutamyltranspeptidase–Activated Fluorescent Probe

Science Translational Medicine  23 Nov 2011:
Vol. 3, Issue 110, pp. 110ra119
DOI: 10.1126/scitranslmed.3002823

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No Tumor Left Behind

Although quick action with spray paint usually conjures images of a schoolboy prank, researchers now show that spray painting of tiny tumors might save lives by illuminating these troublemakers that are often overlooked by the naked eye.

Ovarian cancer is a deadly gynecological disease, considering its propensity for invading the peritoneal cavity and depositing tumors throughout. Surgeons can miss these disseminated tumors during surgical removal of cancerous lesions, owing to their small size (~1 mm) and unclear borders. To help surgeons visualize and eliminate these clandestine killers, Urano et al. have developed a small-molecule aminopeptidase probe that fluoresces upon contact with cancer cells. The probe—γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG)—is intramolecularly caged, so that it is quenched (nonfluorescent) in its “off” state. When the probe encounters cancer cells, which overexpress the enzyme γ-glutamyltranspeptidase (GGT), the gGlu is cleaved, simultaneously turning “on” the fluorescent HMRG. Urano and colleagues first tested the probe in 11 human ovarian cancer cell lines in vitro and observed rapid fluorescence within 10 min after addition of the imaging agent to the cell cultures. They next moved into several mouse models of disseminated human peritoneal ovarian cancer, using a spray formulation of the probe that allowed the researchers to topically apply the probe during surgery or endoscopy. Within 1 min of spraying the tumors, gGlu-HMRG was enzymatically cleaved, revealing a bright fluorescent region of the peritoneal cavity in which the cancerous lesions were located. These small nodules were quickly and completely removed from living animals with forceps, demonstrating the power of rapid fluorescence-guided tumor resection.

This gGlu-based fluorescent probe as well as several other aminopeptidase–based reagents identified by the authors could help surgeons to track down tiny tumors dispersed throughout body cavities, ensuring that no residual tumor is left behind. Complete obliteration of disseminated tumors should improve cancer outcomes after surgery.