The incidence of esophageal
adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of
Barrett's esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface
fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the
peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2. We labeled this
peptide with a near-infrared fluorophore
Cy5.5, and validated the specific binding to FGFR2 overexpressed in cells in vitro. We found high affinity kd = 68 nM and rapid binding k = 0.16 min-1 (6.2 min). In human esophageal specimens, we found significantly greater
peptide binding to high-grade dysplasia (HGD) versus either BE or normal squamous epithelium, and good correlation with anti-FGFR2 antibody. We also observed significantly greater
peptide binding to excised specimens of
esophageal squamous cell carcinoma and
gastric cancer compared to normal mucosa. These results demonstrate potential for this FGFR2
peptide to be used as a clinical imaging agent to guide tissue biopsy and improve methods for early detection of EAC and potentially other epithelial-derived
cancers.