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Nat Med. 2015 Aug;21(8):955-61. doi: 10.1038/nm.3641. Epub 2015 Jul 13.

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

Author information

1
Centre for Human Drug Research, Leiden, the Netherlands.
2
GE Healthcare, Oslo, Norway.
3
GE Global Research Centre, Niskayuna, New York, USA.
4
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
5
Pathology Diagnostics Ltd., St. John's Innovation Centre, Cambridge, UK.
6
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
7
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
8
GE Healthcare, Amersham, UK.

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.

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PMID:
26168295
DOI:
10.1038/nm.3641
[Indexed for MEDLINE]

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