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.

Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study

“…To reduce background fluorescence and autofluorescence and increase tissue penetration, near-infrared fluorescent (NIRF) dyes must be used that have excitation wavelengths between 700 and 900 nm (27). More recently, Burggraaf and colleagues demonstrated c-met-targeted endoscopy fluorescence imaging in humans using a fluorescent dye of 650 nm (28), whereas Rosenthal and colleagues have demonstrated the feasibility of using the therapeutic mAb cetuximab targeting EGFR as the targeting moiety of an NIRF tracer in patients with head and neck cancer (29). In addition, the clinical application of a proteaseactivatable tracer has been reported in patients with soft tissue sarcoma and breast cancer (30).…”

Detection of Micrometastases Using SPECT/Fluorescence Dual-Modality Imaging in a CEA-Expressing Tumor Model

“…Also, one should consider that the sensitivity of real-time fluorescence imaging scanners used in the clinic differs significantly from the scanners that were used in this study. Several reports have shown the feasibility of targeted fluorescence imaging of cancer in humans (8,35,36); however, the technique is still in its infancy and has to be optimized before it can be used in clinical practice. Another consideration is that the spatial resolution of images acquired with clinical PET scanners is higher than the resolution of SPECT scanners.…”

Emerging Opportunities for c-MET Visualization in the Clinic

“…Recently, GE-137, a fluorescent c-MET probe of which the targeting moiety is based on the same peptide used by Arulappu et al, was successfully applied to detect polyps in individuals at risk for colorectal cancer. These individuals underwent regular screening colonoscopies and GE-137 served as an add-on red-flag fluorescent imaging technique (22). Benefits of this strategy compared with radionuclidebased imaging are a less costly infrastructure and availability of off the shelf nonradioactive tracers.…”