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Hartmans, E.* ; Tjalma, J.J.J.* ; Linssen, M.D.* ; Allende, P.B.G. ; Koller, M.* ; Jorritsma-Smit, A.* ; Nery, M.e.S.d.O.* ; Elias, S.G.* ; Karrenbeld, A.* ; de Vries, E.G.E.* ; Kleibeuker, J.H.* ; van Dam, G.M.* ; Robinson, D.J.* ; Ntziachristos, V. ; Nagengast, W.B.*

Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy.

Theranostics 8, 1458-1467 (2018)

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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.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.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.signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas.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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