2872 - Non-Invasive Imaging of Acute Radiation-Induced Esophagitis by Targeting CXCR4

J. Pei¹, J. Yu², and J. Liu³; ¹Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ²Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, ³Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China

Purpose/Objective(s): Acute radiation-induced esophagitis (ARIE) is a common side effect and dose-limiting factor of radiotherapy for thoracic tumors and we currently lack established means for the early detection of ARIE. Increased expression of C-X-C-chemokine-receptor-type-4 (CXCR4) was observed in ARIE mice model, suggesting that CXCR4 may serve as a potential biomarker of ARIE. The hypothesis is that non-invasive imaging of ¹⁸F labeled polypeptide (QHY-04) targeting CXCR4 enables early detection of ARIE. Materials/

Methods: An ARIE model was constructed using a high-dose single radiotherapy. Small animal Magnetic Resonance Imaging (MRI) was conducted on day 3, 5, 7 and 15 after radiotherapy. ARIE animals were scanned with [¹⁸F]AlF-NOTA-QHY-04 PET/CT and [¹⁸F] FDG PET/CT at various time-points post radiotherapy. Dynamic, in vivo blocking study, RNA sequencing analysis, flow cytometry and histopathological studies were performed on the day of peak uptake. Changes of esophageal [¹⁸F]AlF-NOTA-QHY-04 uptake were analyzed before and during RT in patients with thoracic tumors.
Results: Enhanced signal intensity of the esophagus and surrounding tissues was observed in ARIE mice compared with normal mice by MRI. Pathological manifestations of radiation induced esophagitis including congestion of blood vessels, detachment of the esophageal epithelium and layer distortion due to necrosis was confirmed by H&E staining. RNA sequencing analysis identified CXCR4 as a potential target of ARIE and significant up-regulation of CXCR4 in the ARIE mice was verified by immunofluorescence staining. Significantly increased [¹⁸F]AlF-NOTA-QHY-04 uptake in the irradiated esophagus in comparison with normal esophagus was observed on day 5 post radiotherapy while no obvious [¹⁸F] FDG uptake was shown on day 4 to day 8 post radiotherapy. Simultaneously injection with an excess of non-radiolabeled precursor significantly blocked esophagus uptake. The feasibility of [¹⁸F]AlF-NOTA-QHY-04 PET/CT imaging for detecting ARIE was further verified in a rat model of ARIE. Immune cell infiltration and flow cytometry identified CXCR4 positive neutrophils and monocytes as the major source of the radiotracer detected by PET. Esophageal uptakes were significantly increased in patients with thoracic tumors after RT compared with esophageal [¹⁸F]AlF-NOTA-QHY-04 uptakes before radiotherapy.
Conclusion: [¹⁸F]AlF-NOTA-QHY-04 PET/CT can detect ARIE non-invasively and earlier than [¹⁸F] FDG PET/CT in experimental animal models. Clinical studies verified its feasibility, suggesting the clinical potential of [¹⁸F]AlF-NOTA-QHY-04 as a PET/CT tracer for early monitoring of ARIE.