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Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met

2015; Nature Portfolio; Volume: 21; Issue: 8 Linguagem: Inglês

10.1038/nm.3641

1546-170X

Jacobus Burggraaf, Ingrid M. C. Kamerling, Paul B. Gordon, Lenneke Schrier, Marieke L. de Kam, Andrea J. Kales, Ragnar Bendiksen, Bård Indrevoll, Roger M. Bjerke, Siver Andreas Moestue, Siavash Yazdanfar, Alexandra M. J. Langers, Marit Swaerd-Nordmo, Geir Torheim, Madhuri Warren, Hans Morreau, Philip W. Voorneveld, Tessa Buckle, Fijs W. B. van Leeuwen, Liv-Ingrid Ødegårdstuen, Grethe Tang Dalsgaard, Andrew Healey, James C.H. Hardwick,

Colorectal Cancer Treatments and Studies

Intravenous administration of a fluorescently labeled c-Met–binding peptide enables visualization of polyps not detected using white light. Colon cancer prevention currently relies on colonoscopy using white light to detect and remove polyps, but small and flat polyps are difficult to detect and frequently missed when using this technique. Fluorescence colonoscopy combined with a fluorescent probe specific for a polyp biomarker may improve polyp detection. Here we describe GE-137, a water-soluble probe consisting of a 26–amino acid cyclic peptide that binds the human tyrosine kinase c-Met conjugated to a fluorescent cyanine dye. Intravenous administration of GE-137 leads to its accumulation specifically in c-Met–expressing tumors in mice, and it is safe and well tolerated in humans. Fluorescence colonoscopy in patients receiving intravenous GE-137 enabled visualization of all neoplastic polyps that were visible with white light (38), as well as an additional nine polyps that were not visible with white light. This first-in-human pilot study shows that molecular imaging using an intravenous fluorescent agent specific for c-Met is feasible and safe, and that it may enable the detection of polyps missed by other techniques.