Purpose: Acute radiation-induced esophagitis (ARIE) is a common and dose-limiting adverse reaction associated with radiotherapy for thoracic tumors. mRNA sequencing identified CXCR4 as a potential target for noninvasive imaging of ARIE and significant up-regulation of CXCR4 expression was further confirmed in ARIE experimental animal model and clinical samples. This research investigated the feasibility of targeting CXCR4 for the diagnosis and treatment of ARIE.
Methods: ARIE models were established, and magnetic resonance imaging was performed. Dynamic, blocking, histopathological studies, mRNA-sequencing and flow cytometry were conducted. The feasibility of an 18F-labeled polypeptide (QHY-04) targeting CXCR4 for detecting ARIE was validated. CXCR4 blockade using AMD3100 was applied immediately post radiotherapy.
Results: Increased signal intensity in the esophagus and surrounding tissues was observed in ARIE models, with clinical manifestations confirmed by H&E staining. Immunofluorescence staining demonstrated significant CXCR4 up-regulation. Significantly increased [18F]AlF-NOTA-QHY-04 uptake in the irradiated esophagus was observed via PET imaging. Immune cell infiltration and flow cytometry identified CXCR4-positive neutrophils and monocytes as the primary source of the radiotracer. AMD3100-mediated CXCR4 blockade significantly reduced ARIE.
Conclusion: CXCR4-targeted PET/CT facilitates noninvasive detection of ARIE in experimental animal models. CXCR4 blockade mitigates ARIE, highlighting CXCR4 as a promising theranostic target of ARIE.
Keywords: Acute radiation-induced esophagitis; C-X-C-chemokine-receptor-type-4; Molecular imaging.
Copyright © 2025. Published by Elsevier B.V.