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To improve detection of esophageal (pre)malignant lesions during surveillance endoscopy of patients at risk of developing malignancies, for example in Barrett's Esophagus (BE), there is a need for better endoscopic visualization and the ability for targeted biopsies. Optical molecular imaging of neoplasia associated biomarkers could form a promising technique to accommodate this need. It is known that the biomarker c-Met is overexpressed in dysplastic and neoplastic areas in BE segments versus normal tissue and has proven to be a valid target for molecular imaging.
Edinburgh Molecular Imaging Ltd (EMI) has developed a fluorescent tracer specifically targeting c-Met by labeling a small peptide to a fluorescent fluorophore: 'EMI-137'. The investigators hypothesize that when EMI-137 is administered intravenously, it accumulates in c-Met expressing high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC), enabling (early) cancer visualization using a newly developed fluorescent fiber-bundle. This hypothesis will be tested in the current pilot intervention study.
See brief summary.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IV-tracer EMI-137 | Experimental |
|
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IV-administation of EMI-137 | Drug | Intravenous administration of 0.13 mg/kg of the fluorescent tracer EMI-137 approximately 2.5 hours prior to the endoscopy procedure. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Tumor-to-background ratio that allows the in vivo detection of (pre)malignant lesions in patients with Barrett's Esophagus using molecular fluorescence endoscopy. | Calculation of the in vivo tumor-to-background ratio (> 1.5) based on fluorescence intensities in (pre)malignant lesions compared to surrounding healthy esophageal tissue. | Day 1 |
| Safety: the number of participants with symptoms or changes in vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to administration of EMI-137. | Up to day 3 |
| Measure | Description | Time Frame |
|---|---|---|
| The correlation of fluorescence signals to histopathology from (pre)malignant lesions and surrounding normal esophageal tissue. | Up to 1 year | |
| Identification of fluorescence lesions and correlation with histopathology on subsequent biopsies in the resection surface after endoscopic mucosal resection. |
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Inclusion Criteria:
Age ≥ 18 years, eligible for a diagnostic and/or therapeutic endoscopy;
At least a suspicion of low grade dysplasia (LGD) based on a prior endoscopy;
World Health Organization (WHO) performance score of 0-2;
Written informed consent;
Mentally competent person that is able and willing to comply with study procedures;
For female subjects who are of childbearing potential, are premenopausal with intact reproductive organs or are less than 2 years post-menopausal:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| W.B. Nagengast, MD, PhD, PharmD | University Medical Center Groningen | Principal Investigator |
| G.M. van Dam, MD, PhD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | 9713GZ | Netherlands |
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| ID | Term |
|---|---|
| D001471 | Barrett Esophagus |
| D004938 | Esophageal Neoplasms |
| ID | Term |
|---|---|
| D011230 | Precancerous Conditions |
| D009369 | Neoplasms |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
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| Molecular Fluorescence Endoscopy platform | Device | A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working-channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the endoscopic resection, during the same endoscopy procedure. |
|
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| Up to 1 year |
| Quantification of fluorescence signals in vivo and ex vivo of (pre)malignant lesions and normal esophageal tissue using multi-diameter single-fiber reflectance single-fiber fluorescence (MDSFR-SFF) spectroscopy. | Up to 1 year |
| Visualization of the localization and distribution patterns of EMI-137 in the esophagus using ex vivo fluorescence microscopy. | Up to 1 year |
| D004066 |
| Digestive System Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |