Publication

Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection

Tjalma, J. J., Garcia-Allende, P. B., Hartmans, E., Terwisscha Van Scheltinga, A. G., Boersma-van Ek, W., Glatz, J., Koch, M., van Herwaarden, Y. J., Bisseling, T. M., Nagtegaal, I. D., Timmer-Bosscha, H., Koornstra, J. J., Karrenbeld, A., Kleibeuker, J. H., van Dam, G. M., Ntziachristos, V. & Nagengast, W. B., 17-Dec-2015, In : Journal of Nuclear Medicine. 57, 3, p. 480-485 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Tjalma, J. J., Garcia-Allende, P. B., Hartmans, E., Terwisscha Van Scheltinga, A. G., Boersma-van Ek, W., Glatz, J., ... Nagengast, W. B. (2015). Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. Journal of Nuclear Medicine, 57(3), 480-485. https://doi.org/10.2967/jnumed.115.166975

Author

Tjalma, Jolien J. ; Garcia-Allende, P. Beatriz ; Hartmans, Elmire ; Terwisscha Van Scheltinga, A.G. ; Boersma-van Ek, Wytske ; Glatz, Juergen ; Koch, Maximilian ; van Herwaarden, Yasmijn J. ; Bisseling, Tanya M. ; Nagtegaal, Iris D. ; Timmer-Bosscha, Hetty ; Koornstra, Jan Jacob ; Karrenbeld, Arend ; Kleibeuker, Jan H. ; van Dam, Gooitzen M. ; Ntziachristos, Vasilis ; Nagengast, Wouter B. / Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. In: Journal of Nuclear Medicine. 2015 ; Vol. 57, No. 3. pp. 480-485.

Harvard

Tjalma, JJ, Garcia-Allende, PB, Hartmans, E, Terwisscha Van Scheltinga, AG, Boersma-van Ek, W, Glatz, J, Koch, M, van Herwaarden, YJ, Bisseling, TM, Nagtegaal, ID, Timmer-Bosscha, H, Koornstra, JJ, Karrenbeld, A, Kleibeuker, JH, van Dam, GM, Ntziachristos, V & Nagengast, WB 2015, 'Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection', Journal of Nuclear Medicine, vol. 57, no. 3, pp. 480-485. https://doi.org/10.2967/jnumed.115.166975

Standard

Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. / Tjalma, Jolien J.; Garcia-Allende, P. Beatriz; Hartmans, Elmire; Terwisscha Van Scheltinga, A.G.; Boersma-van Ek, Wytske; Glatz, Juergen; Koch, Maximilian; van Herwaarden, Yasmijn J.; Bisseling, Tanya M.; Nagtegaal, Iris D.; Timmer-Bosscha, Hetty; Koornstra, Jan Jacob; Karrenbeld, Arend; Kleibeuker, Jan H.; van Dam, Gooitzen M.; Ntziachristos, Vasilis; Nagengast, Wouter B.

In: Journal of Nuclear Medicine, Vol. 57, No. 3, 17.12.2015, p. 480-485.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Tjalma JJ, Garcia-Allende PB, Hartmans E, Terwisscha Van Scheltinga AG, Boersma-van Ek W, Glatz J et al. Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection. Journal of Nuclear Medicine. 2015 Dec 17;57(3):480-485. https://doi.org/10.2967/jnumed.115.166975


BibTeX

@article{ba70365fb56440fa86946fe0032a798c,
title = "Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection",
abstract = "Small and flat adenomas are known to carry a high miss-rate during standard white-light endoscopy. Increased detection rate may be achieved by molecular fluorescence endoscopy with targeted near infrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR)-targeted fluorescent tracers during ex vivo colonoscopy with an NIR endoscopy platform. Methods: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples-48 sessile serrated adenomas/polyps, 70 sporadic high-grade dysplastic adenomas, and 19 hyperplastic polyps and tissue derived from patients with Lynch syndrome-78 low-grade dysplastic adenomas, 57 high-grade dysplastic adenomas, and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116(luc) tumors received intravenous bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW, or sodium chloride. Three days later, 8 resected HCT116(luc) tumors (2-5 mm) were stitched into 1 freshly resected human colon specimen and followed by an ex vivo molecular fluorescence colonoscopy procedure. Results: Immunohistochemistry showed high VEGF-A expression in 79{\%}-96{\%} and high EGFR expression in 51{\%}-69{\%} of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions, compared with the adjacent normal colon crypts. During ex vivo molecular fluorescence endoscopy, all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing, respectively, stromal and cell membrane fluorescence. Conclusion: VEGF-A is a promising target for molecular fluorescence endoscopy because it showed a high protein expression, especially in sessile serrated adenomas/polyps and Lynch syndrome. We demonstrated the feasibility to visualize small tumors in real time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field red flag technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach.",
keywords = "optical imaging, molecular imaging, vascular endothelial growth factor A, near-infrared fluorescence, endoscopy, ADENOMA-CARCINOMA SEQUENCE, COLONOSCOPIC SURVEILLANCE, FACTOR RECEPTOR, IN-VIVO, ANGIOGENIC SWITCH, LYNCH-SYNDROME, CANCER, ENDOMICROSCOPY, ANTIBODIES, DYSPLASIA",
author = "Tjalma, {Jolien J.} and Garcia-Allende, {P. Beatriz} and Elmire Hartmans and {Terwisscha Van Scheltinga}, A.G. and {Boersma-van Ek}, Wytske and Juergen Glatz and Maximilian Koch and {van Herwaarden}, {Yasmijn J.} and Bisseling, {Tanya M.} and Nagtegaal, {Iris D.} and Hetty Timmer-Bosscha and Koornstra, {Jan Jacob} and Arend Karrenbeld and Kleibeuker, {Jan H.} and {van Dam}, {Gooitzen M.} and Vasilis Ntziachristos and Nagengast, {Wouter B.}",
year = "2015",
month = "12",
day = "17",
doi = "10.2967/jnumed.115.166975",
language = "English",
volume = "57",
pages = "480--485",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "SOC NUCLEAR MEDICINE INC",
number = "3",

}

RIS

TY - JOUR

T1 - Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection

AU - Tjalma, Jolien J.

AU - Garcia-Allende, P. Beatriz

AU - Hartmans, Elmire

AU - Terwisscha Van Scheltinga, A.G.

AU - Boersma-van Ek, Wytske

AU - Glatz, Juergen

AU - Koch, Maximilian

AU - van Herwaarden, Yasmijn J.

AU - Bisseling, Tanya M.

AU - Nagtegaal, Iris D.

AU - Timmer-Bosscha, Hetty

AU - Koornstra, Jan Jacob

AU - Karrenbeld, Arend

AU - Kleibeuker, Jan H.

AU - van Dam, Gooitzen M.

AU - Ntziachristos, Vasilis

AU - Nagengast, Wouter B.

PY - 2015/12/17

Y1 - 2015/12/17

N2 - Small and flat adenomas are known to carry a high miss-rate during standard white-light endoscopy. Increased detection rate may be achieved by molecular fluorescence endoscopy with targeted near infrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR)-targeted fluorescent tracers during ex vivo colonoscopy with an NIR endoscopy platform. Methods: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples-48 sessile serrated adenomas/polyps, 70 sporadic high-grade dysplastic adenomas, and 19 hyperplastic polyps and tissue derived from patients with Lynch syndrome-78 low-grade dysplastic adenomas, 57 high-grade dysplastic adenomas, and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116(luc) tumors received intravenous bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW, or sodium chloride. Three days later, 8 resected HCT116(luc) tumors (2-5 mm) were stitched into 1 freshly resected human colon specimen and followed by an ex vivo molecular fluorescence colonoscopy procedure. Results: Immunohistochemistry showed high VEGF-A expression in 79%-96% and high EGFR expression in 51%-69% of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions, compared with the adjacent normal colon crypts. During ex vivo molecular fluorescence endoscopy, all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing, respectively, stromal and cell membrane fluorescence. Conclusion: VEGF-A is a promising target for molecular fluorescence endoscopy because it showed a high protein expression, especially in sessile serrated adenomas/polyps and Lynch syndrome. We demonstrated the feasibility to visualize small tumors in real time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field red flag technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach.

AB - Small and flat adenomas are known to carry a high miss-rate during standard white-light endoscopy. Increased detection rate may be achieved by molecular fluorescence endoscopy with targeted near infrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR)-targeted fluorescent tracers during ex vivo colonoscopy with an NIR endoscopy platform. Methods: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples-48 sessile serrated adenomas/polyps, 70 sporadic high-grade dysplastic adenomas, and 19 hyperplastic polyps and tissue derived from patients with Lynch syndrome-78 low-grade dysplastic adenomas, 57 high-grade dysplastic adenomas, and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116(luc) tumors received intravenous bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW, or sodium chloride. Three days later, 8 resected HCT116(luc) tumors (2-5 mm) were stitched into 1 freshly resected human colon specimen and followed by an ex vivo molecular fluorescence colonoscopy procedure. Results: Immunohistochemistry showed high VEGF-A expression in 79%-96% and high EGFR expression in 51%-69% of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions, compared with the adjacent normal colon crypts. During ex vivo molecular fluorescence endoscopy, all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing, respectively, stromal and cell membrane fluorescence. Conclusion: VEGF-A is a promising target for molecular fluorescence endoscopy because it showed a high protein expression, especially in sessile serrated adenomas/polyps and Lynch syndrome. We demonstrated the feasibility to visualize small tumors in real time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field red flag technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach.

KW - optical imaging

KW - molecular imaging

KW - vascular endothelial growth factor A

KW - near-infrared fluorescence

KW - endoscopy

KW - ADENOMA-CARCINOMA SEQUENCE

KW - COLONOSCOPIC SURVEILLANCE

KW - FACTOR RECEPTOR

KW - IN-VIVO

KW - ANGIOGENIC SWITCH

KW - LYNCH-SYNDROME

KW - CANCER

KW - ENDOMICROSCOPY

KW - ANTIBODIES

KW - DYSPLASIA

U2 - 10.2967/jnumed.115.166975

DO - 10.2967/jnumed.115.166975

M3 - Article

VL - 57

SP - 480

EP - 485

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 3

ER -

ID: 34300701