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

PURPOSE: Radiation-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 transforming growth factor β after radiation injury. This study aimed to investigate integrin αvβ6-targeted positron emission tomography (PET) imaging ([64Cu]Cu-αvβ6-BP) to study RIPF development in vivo.

METHODS AND MATERIALS: We 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/computed tomography images were acquired 1 hour postinjection of 11.1 MBq of [64Cu]Cu-αvβ6-BP. Animals were imaged for 8 weeks in the focal RIPF model and 6 months in the whole lung RIPF model. Immunohistochemistry for integrin αvβ6 and trichrome staining were performed.

RESULTS

In the focal RIPF model, there was focal uptake of [64Cu]Cu-αvβ6-BP in the irradiated region at week 4 that progressively increased at weeks 6 and 8. In the whole lung RIPF model, minimal uptake of the probe was observed at 4 months post-radiation therapy, which significantly increased at months 5 and 6. Expression of integrin αvβ6 was validated histologically by immunohistochemistry in both models.

CONCLUSIONS

Integrin αvβ6-targeted PET imaging using [64Cu]Cu-αvβ6-BP can serve as a useful tool to identify RIPF in vivo.