1. Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met
- Author
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James C. H. Hardwick, Philip W. Voorneveld, Marieke L. de Kam, Hans Morreau, Andrew Healey, Roger Bjerke, Andrea J Kales, Ragnar Bendiksen, Paul Gordon, Geir Torheim, Siver Andreas Moestue, Grethe Tang Dalsgaard, Marit Swaerd-Nordmo, Bard Indrevoll, Fijs W. B. van Leeuwen, Ingrid M C Kamerling, Jacobus Burggraaf, Lenneke Schrier, Liv-Ingrid Odegardstuen, Tessa Buckle, Alexandra M. J. Langers, Siavash Yazdanfar, and Madhuri V Warren
- Subjects
Male ,Pathology ,medicine.medical_specialty ,C-Met ,Colorectal cancer ,Molecular Sequence Data ,Intestinal polyp ,Colonoscopy ,Peptide ,Peptides, Cyclic ,General Biochemistry, Genetics and Molecular Biology ,Fluorescence ,chemistry.chemical_compound ,Mice ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Amino Acid Sequence ,chemistry.chemical_classification ,Mice, Inbred BALB C ,medicine.diagnostic_test ,business.industry ,Intestinal Polyps ,General Medicine ,Proto-Oncogene Proteins c-met ,medicine.disease ,digestive system diseases ,Macaca fascicularis ,chemistry ,Biomarker (medicine) ,Female ,Molecular imaging ,business ,Colorectal Neoplasms - Abstract
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.
- Published
- 2015