Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas. Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME. Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas ( < 3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas. Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas.

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Keywords Near-infrared fluorescence, Optical molecular imaging, Spectroscopy, Vascular endothelial growth factor a
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Journal Theranostics
Hartmans, E. (Elmire), Tjalma, J.J.J. (Jolien J.J.), Linssen, M.D. (Matthijs D.), Allende, P.B.G. (Pilar Beatriz Garcia), Koller, M. (Marjory), Jorritsma-Smit, A. (Annelies), … Nagengast, W.B. (Wouter B.). (2018). Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy. Theranostics, 8(6), 1458–1467. doi:10.7150/thno.22033