Publication

C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies

de Jongh, S. J., Voskuil, F. J., Schmidt, I., Karrenbeld, A., Kats-Ugurlu, G., Meersma, G. J., Westerhof, J., Witjes, M. J. H., van Dam, G. M., Robinson, D. J. & Nagengast, W. B., 2020, In : Theranostics. 10, 12, p. 5357-5367 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

de Jongh, S. J., Voskuil, F. J., Schmidt, I., Karrenbeld, A., Kats-Ugurlu, G., Meersma, G. J., Westerhof, J., Witjes, M. J. H., van Dam, G. M., Robinson, D. J., & Nagengast, W. B. (2020). C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies. Theranostics, 10(12), 5357-5367. https://doi.org/10.7150/thno.42224

Author

de Jongh, Steven J ; Voskuil, Floris J ; Schmidt, Iris ; Karrenbeld, Arend ; Kats-Ugurlu, Gursah ; Meersma, Gert Jan ; Westerhof, Jessie ; Witjes, Max J H ; van Dam, Gooitzen M ; Robinson, Dominic J ; Nagengast, Wouter B. / C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies. In: Theranostics. 2020 ; Vol. 10, No. 12. pp. 5357-5367.

Harvard

de Jongh, SJ, Voskuil, FJ, Schmidt, I, Karrenbeld, A, Kats-Ugurlu, G, Meersma, GJ, Westerhof, J, Witjes, MJH, van Dam, GM, Robinson, DJ & Nagengast, WB 2020, 'C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies', Theranostics, vol. 10, no. 12, pp. 5357-5367. https://doi.org/10.7150/thno.42224

Standard

C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies. / de Jongh, Steven J; Voskuil, Floris J; Schmidt, Iris; Karrenbeld, Arend; Kats-Ugurlu, Gursah; Meersma, Gert Jan; Westerhof, Jessie; Witjes, Max J H; van Dam, Gooitzen M; Robinson, Dominic J; Nagengast, Wouter B.

In: Theranostics, Vol. 10, No. 12, 2020, p. 5357-5367.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

de Jongh SJ, Voskuil FJ, Schmidt I, Karrenbeld A, Kats-Ugurlu G, Meersma GJ et al. C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies. Theranostics. 2020;10(12):5357-5367. https://doi.org/10.7150/thno.42224


BibTeX

@article{6e9c190e160346f19c286a94b74ed0e2,
title = "C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies",
abstract = "Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a 'red-flag' endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett's Esophagus (BE) and report several outcome parameters for early phase FME studies. Methods: FME was performed in 15 Barrett's neoplasia patients. EMI-137 was administered to three cohorts of five patients: 0.13 mg/kg intravenously (IV); 0.09 mg/kg IV or topically at a dose of 200 μg/cm BE (n=1) or 100 μg/cm BE (n=4). Fluorescence was visualized in vivo, quantified in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlated to histopathology and immunohistochemistry. EMI-137 localization was assessed using fluorescence microscopy. Results: FME using different IV and topical doses of EMI-137 appeared to be safe and correctly identified 16/18 lesions, although modest target-to-background ratios were observed (median range of 1.12-1.50). C-Met overexpression varied between lesions, while physiological expression in the stomach-type epithelium was observed. Microscopically, EMI-137 accumulated around the neoplastic cell membranes. We identified several outcome parameters important for the validation of EMI-137 for FME: 1) the optimal administration route; 2) optimal dose and safety; 3) in vivo FME contrast; 4) quantification of intrinsic fluorescence; 5) ex vivo correlation of fluorescence, histopathology and target expression; and 6) microscopic tracer distribution. Conclusions: C-Met targeted FME using EMI-137 may not be the ideal combination to improve BE surveillance endoscopies, however the identified outcome parameters may serve as a valuable guidance for designing and performing future early phase clinical FME studies, independent of which fluorescent tracer is investigated.",
keywords = "Structured roadmap, standardized fluorescence molecular endoscopy methodology, Barrett's esophagus, EMI-137 targeting c-Met, IMAGING AGENTS, ADENOMAS, CANCER",
author = "{de Jongh}, {Steven J} and Voskuil, {Floris J} and Iris Schmidt and Arend Karrenbeld and Gursah Kats-Ugurlu and Meersma, {Gert Jan} and Jessie Westerhof and Witjes, {Max J H} and {van Dam}, {Gooitzen M} and Robinson, {Dominic J} and Nagengast, {Wouter B}",
note = "{\textcopyright} The author(s).",
year = "2020",
doi = "10.7150/thno.42224",
language = "English",
volume = "10",
pages = "5357--5367",
journal = "Theranostics",
issn = "1838-7640",
publisher = "IVYSPRING INT PUBL",
number = "12",

}

RIS

TY - JOUR

T1 - C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies

AU - de Jongh, Steven J

AU - Voskuil, Floris J

AU - Schmidt, Iris

AU - Karrenbeld, Arend

AU - Kats-Ugurlu, Gursah

AU - Meersma, Gert Jan

AU - Westerhof, Jessie

AU - Witjes, Max J H

AU - van Dam, Gooitzen M

AU - Robinson, Dominic J

AU - Nagengast, Wouter B

N1 - © The author(s).

PY - 2020

Y1 - 2020

N2 - Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a 'red-flag' endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett's Esophagus (BE) and report several outcome parameters for early phase FME studies. Methods: FME was performed in 15 Barrett's neoplasia patients. EMI-137 was administered to three cohorts of five patients: 0.13 mg/kg intravenously (IV); 0.09 mg/kg IV or topically at a dose of 200 μg/cm BE (n=1) or 100 μg/cm BE (n=4). Fluorescence was visualized in vivo, quantified in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlated to histopathology and immunohistochemistry. EMI-137 localization was assessed using fluorescence microscopy. Results: FME using different IV and topical doses of EMI-137 appeared to be safe and correctly identified 16/18 lesions, although modest target-to-background ratios were observed (median range of 1.12-1.50). C-Met overexpression varied between lesions, while physiological expression in the stomach-type epithelium was observed. Microscopically, EMI-137 accumulated around the neoplastic cell membranes. We identified several outcome parameters important for the validation of EMI-137 for FME: 1) the optimal administration route; 2) optimal dose and safety; 3) in vivo FME contrast; 4) quantification of intrinsic fluorescence; 5) ex vivo correlation of fluorescence, histopathology and target expression; and 6) microscopic tracer distribution. Conclusions: C-Met targeted FME using EMI-137 may not be the ideal combination to improve BE surveillance endoscopies, however the identified outcome parameters may serve as a valuable guidance for designing and performing future early phase clinical FME studies, independent of which fluorescent tracer is investigated.

AB - Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a 'red-flag' endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett's Esophagus (BE) and report several outcome parameters for early phase FME studies. Methods: FME was performed in 15 Barrett's neoplasia patients. EMI-137 was administered to three cohorts of five patients: 0.13 mg/kg intravenously (IV); 0.09 mg/kg IV or topically at a dose of 200 μg/cm BE (n=1) or 100 μg/cm BE (n=4). Fluorescence was visualized in vivo, quantified in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlated to histopathology and immunohistochemistry. EMI-137 localization was assessed using fluorescence microscopy. Results: FME using different IV and topical doses of EMI-137 appeared to be safe and correctly identified 16/18 lesions, although modest target-to-background ratios were observed (median range of 1.12-1.50). C-Met overexpression varied between lesions, while physiological expression in the stomach-type epithelium was observed. Microscopically, EMI-137 accumulated around the neoplastic cell membranes. We identified several outcome parameters important for the validation of EMI-137 for FME: 1) the optimal administration route; 2) optimal dose and safety; 3) in vivo FME contrast; 4) quantification of intrinsic fluorescence; 5) ex vivo correlation of fluorescence, histopathology and target expression; and 6) microscopic tracer distribution. Conclusions: C-Met targeted FME using EMI-137 may not be the ideal combination to improve BE surveillance endoscopies, however the identified outcome parameters may serve as a valuable guidance for designing and performing future early phase clinical FME studies, independent of which fluorescent tracer is investigated.

KW - Structured roadmap

KW - standardized fluorescence molecular endoscopy methodology

KW - Barrett's esophagus

KW - EMI-137 targeting c-Met

KW - IMAGING AGENTS

KW - ADENOMAS

KW - CANCER

U2 - 10.7150/thno.42224

DO - 10.7150/thno.42224

M3 - Article

C2 - 32373217

VL - 10

SP - 5357

EP - 5367

JO - Theranostics

JF - Theranostics

SN - 1838-7640

IS - 12

ER -

ID: 124921222