title: Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met.
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.
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Jacobus
authors.initials: J
authors.lastname: Burggraaf
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Ingrid M C
authors.initials: IM
authors.lastname: Kamerling
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Gordon
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Lenneke
authors.initials: L
authors.lastname: Schrier
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Marieke L
authors.initials: ML
authors.lastname: de Kam
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Kales
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Bendiksen
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Bård
authors.initials: B
authors.lastname: Indrevoll
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Bjerke
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Siver A
authors.initials: SA
authors.lastname: Moestue
authors.affiliation: GE Global Research Centre, Niskayuna, New York, USA.
authors.forename: Siavash
authors.identifier: 0000000327686199
authors.initials: S
authors.lastname: Yazdanfar
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Alexandra M J
authors.initials: AM
authors.lastname: Langers
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Swaerd-Nordmo
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Torheim
authors.affiliation: Pathology Diagnostics Ltd., St. John's Innovation Centre, Cambridge, UK.
authors.forename: Madhuri V
authors.identifier: 0000000191843334
authors.initials: MV
authors.lastname: Warren
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Philip W
authors.identifier: 0000000238814435
authors.initials: PW
authors.lastname: Voorneveld
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: Buckle
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Fijs W B
authors.initials: FW
authors.lastname: van Leeuwen
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Liv-Ingrid
authors.initials: LI
authors.lastname: Ødegårdstuen
authors.affiliation: GE Healthcare, Amersham, UK.
authors.forename: Grethe T
authors.initials: GT
authors.lastname: Dalsgaard
authors.affiliation: GE Healthcare, Oslo, Norway.
authors.forename: Andrew
authors.initials: A
authors.lastname: Healey
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: James C H
authors.initials: JC
authors.lastname: Hardwick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D005260:Female; D005453:Fluorescence; D006801:Humans; D007417:Intestinal Polyps / Q000175:diagnosis*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000187:drug effects*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*
chemical_list: C000595832:GE137 peptide; D010456:Peptides, Cyclic; D019859:Proto-Oncogene Proteins c-met