TY - JOUR
T1 - Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy
AU - Hartmans, Elmire
AU - Tjalma, Jolien J.J.
AU - Linssen, Matthijs D.
AU - Allende, Pilar Beatriz Garcia
AU - Koller, Marjory
AU - Jorritsma-Smit, Annelies
AU - Nery, Mariana e.Silva de Oliveira
AU - Elias, Sjoerd G.
AU - Karrenbeld, Arend
AU - de Vries, Elisabeth G.E.
AU - Kleibeuker, Jan H.
AU - van Dam, Gooitzen M.
AU - Robinson, Dominic J.
AU - Ntziachristos, Vasilis
AU - Nagengast, Wouter B.
N1 - Funding Information:
This work was in part supported by the Dutch Cancer Society (personal grant W.B.N., RUG 2012-5416), Center for Translational Molecular Medicine (project MAMMOTH 03O-201), Royal Netherlands Academy of Arts and Sciences (KNAW, professorship to E.G.E.d.V.), ERC advanced grant OnQview and unrestricted research grants from SurgVision B.V. and Boston Scientific.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Near-infrared fluorescence
KW - Optical molecular imaging
KW - Spectroscopy
KW - Vascular endothelial growth factor a
UR - http://www.scopus.com/inward/record.url?scp=85041585788&partnerID=8YFLogxK
U2 - 10.7150/thno.22033
DO - 10.7150/thno.22033
M3 - Article
AN - SCOPUS:85041585788
SN - 1838-7640
VL - 8
SP - 1458
EP - 1467
JO - Theranostics
JF - Theranostics
IS - 6
ER -