Using Integrin αvβ6–Targeted Positron Emission Tomography Imaging to Longitudinally Monitor Radiation-Induced Pulmonary Fibrosis In Vivo

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PurposeRadiation-induced pulmonary fibrosis (RIPF) is a potentially serious and disabling late complication of radiation therapy. Monitoring RIPF progression is challenging due to the absence of early detection tools and the difficulty in distinguishing RIPF from other lung diseases using standard imaging methods. In the lungs, integrin αvβ6 is crucial in the development of RIPF, acting as a significant activator of TGF-β after radiation injury. This study aims to investigate integrin αvβ6-targeted PET imaging ([64Cu]Cu-αvβ6-BP) to study RIPF development in vivo. Methods and MaterialsWe used a focal RIPF model (70 Gy delivered focally to a 3 mm spot in the lung) and a whole lung RIPF model (14 Gy delivered to the whole lung) in adult C57BL/6J mice. Small animal PET/CT images were acquired 1h post-injection of 11.1 MBq of [64Cu]Cu-αvβ6-BP. Animals were imaged for eight weeks in the focal RIPF model and six months for the whole lung RIPF model. Immunohistochemistry for integrin αvβ6 and trichrome staining were performed. ResultsIn the focal RIPF model, there was focal uptake of [64Cu]Cu-αvβ6-BP in the irradiated region at week four that progressively increased at week 6 and 8. In the whole lung RIPF model, minimal uptake of the probe was observed at four months post-RT, which significantly increased at months five and six. Expression of integrin αvβ6 was validated histologically by immunohistochemistry in both models. ConclusionsIntegrin αvβ6-targeted PET imaging using [64Cu]Cu-αvβ6-BP can serve as a useful tool to identify radiation-induced pulmonary fibrosis in vivo.