CXCR4 is a potential target for diagnostic PET/CT imaging in Barrett's dysplasia and esophageal adenocarcinoma

Introduction: Barrett's Esophagus (BE) represents an early stage in carcinogenesis leading to esophageal adenocarcinoma (EAC). Considerable evidence supports a major role for chronic inflammation and diverse chemokine pathways in the development of BE and EAC. Methods: Here we utilized a IL-1b transgenic mouse model of BE and EAC and human patient imaging to analyse the importance of CXCR4 expressing cells during esophageal carcinogenesis. Results: IL-1b overexpression induces chronic esophageal inflammation and recapitulates the progression to BE and EAC. CXCR4 expression is increased in both epithelial and immune cells during disease progression in pL2-IL1b mice, and also elevated in EAC patient biopsy samples. Specific recruitment of CXCR4-positive (CXCR4+) immune cells correlated with dysplasia progression, suggesting that this immune population may be a key contributor to esophageal carcinogenesis. Similarly, with progression to dysplasia, there were increased numbers of CXCR4+ columnar epithelial cells at the squamocolumnar junction (SCJ). These findings were supported by stronger CXCR4-related signal intensity in ex vivo fluorescence imaging and autoradiography with advanced dysplasia. Pilot CXCR4-directed PET/CT imaging studies in esophageal cancer patients demonstrate the potential utility of CXCR4 imaging for the diagnosis and staging of esophageal cancer. Discussion: In conclusion, the recruitment of CXCR4+ immune cells and expansion of CXCR4+ epithelial cells in esophageal dysplasia and cancer highlight the potential of CXCR4 as a biomarker and molecular target for diagnostic imaging of the tumor microenvironment in EAC. 

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