Targeted Imaging of Esophageal Neoplasia with a Fluorescently Labeled Peptide: First-in-Human Results

Abstract

Esophageal adenocarcinoma is rising rapidly in incidence, and usually develops from Barrett’s esophagus, a precursor condition commonly found in patients with chronic acid reflux. Pre-malignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-humans results show that this targeted imaging agent is safe, and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach.

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett’s esophageal adenocarcinoma

“…Notably, immunoreactivity was observed on the cell plasma membrane, according to the results of Sturm et al 19,20 NPs reach esophageal cancerous tissue but not healthy and Be tissue…”

“…Finally, the heptapeptide ASYNYDA was covalently grafted at the periphery of the NP as a recognition unit to enhance selectivity ( Figure 1). 18,19 In fact, in the literature, this peptide has been isolated from a phage library, labeled with fluorescein isothiocyanate and topically administered on human esophageal ex-vivo specimens. Increased fluorescence intensity at the site of neoplastic mucosa has been clearly observed, showing that the peptide has high sensitivity and specificity for high-grade dysplasia and EAC in BE.…”

Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus

“…There is a need for improved imaging diagnostics to screen for the molecular changes that precede and accompany the onset of esophageal cancer, as well as to investigate the molecular mechanisms of tumor progression in the esophagus. In recent years, several imaging technologies has shown potential to improve cancer detection by providing "optical biopsy" such as confocal laser microendoscopy and fluorescence imaging with molecular contrast agents [7][8][9][10]. Since esophageal cancer originates from the epithelial cells at the lumenal surface of the esophagus, the imaging of cell-surface and tissue biomarkers at these surfaces could be used to monitor disease progression.…”

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

“…First, confocal laser endomicroscopy has shown promising results both preclinically and clinically but has a limited field of view (25)(26)(27). Therefore, confocal laser endomicroscopy is not suitable for screening purposes, as our technique is, but rather a tool for lesion characterization.…”