Theranostics 2020; 10(12):5357-5367. doi:10.7150/thno.42224 This issue Cite

Research Paper

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

Steven J. de Jongh1*, Floris J. Voskuil2*, Iris Schmidt1, Arend Karrenbeld3, Gursah Kats-Ugurlu3, Gert Jan Meersma1, Jessie Westerhof1, Max J.H. Witjes2, Gooitzen M. van Dam4,5, Dominic J. Robinson6, Wouter B. Nagengast1✉

1. Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands;
2. Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, Groningen, The Netherlands;
3. Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands;
4. Department of Surgery and Medical Imaging Center, University Medical Center Groningen, The Netherlands;
5. TRACER EUROPE B.V. / AxelaRx, Groningen, The Netherlands;
6. Center for Optical Diagnostics and Therapy, Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
*Both authors share first authorship

Citation:
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. 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. doi:10.7150/thno.42224. https://www.thno.org/v10p5357.htm
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Abstract

Graphic 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.


Citation styles

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.

ACS
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. 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. DOI: 10.7150/thno.42224.

NLM
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. 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. doi:10.7150/thno.42224. https://www.thno.org/v10p5357.htm

CSE
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. 10(12):5357-5367.

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