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

• Published in: Nature medicine Vol. 21; no. 8; pp. 955 - 961
• Main Authors: Burggraaf, Jacobus, Kamerling, Ingrid M C, Gordon, Paul B, Schrier, Lenneke, de Kam, Marieke L, Kales, Andrea J, Bendiksen, Ragnar, Indrevoll, Bård, Bjerke, Roger M, Moestue, Siver A, Yazdanfar, Siavash, Langers, Alexandra M J, Swaerd-Nordmo, Marit, Torheim, Geir, Warren, Madhuri V, Morreau, Hans, Voorneveld, Philip W, Buckle, Tessa, van Leeuwen, Fijs W B, Ødegårdstuen, Liv-Ingrid, Dalsgaard, Grethe T, Healey, Andrew, Hardwick, James C H
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-08-2015; Nature Publishing Group
• Subjects: 59; 692/308/575; 692/53/2421; 692/699/1503/1504/1885/1393; 692/700/1421/2160; 82; 82/75; Amino Acid Sequence; Amino acids; Animals; Biomarkers; Biomedicine; Cancer Research; Cell Line, Tumor; Colon cancer; Colonoscopy; Colorectal cancer; Colorectal Neoplasms - diagnosis; Diagnosis; Female; Fluorescence; Humans; Infectious Diseases; Intestinal Polyps - diagnosis; Intravenous administration; Macaca fascicularis; Male; Medical diagnosis; Metabolic Diseases; Mice; Mice, Inbred BALB C; Molecular Medicine; Molecular Sequence Data; Neurosciences; Peptides; Peptides, Cyclic - drug effects; Polyps (Pathology); Prevention; Proto-Oncogene Proteins c-met - analysis; technical-report
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.3641

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.