Properties of [¹⁸F]FAPI monitoring of acute radiation pneumonia versus [¹⁸F]FDG in mouse models

Objective: In this study, the uptake characteristics of [F-18]fibroblast activation protein inhibitor (FAPI) molecular imaging probe were investigated in acute radiation pneumonia and lung cancer xenografted mice before and after radiation to assess the future applicability of [F-18]FAPI positron emission tomography/computed tomography (PET/CT) imaging in early radiotherapy response. Methods: Initially, the biodistribution of [F-18]FAPI tracer in vivo were studied in healthy mice at each time-point. A comparison of [F-18]FAPI and [F-18]fluorodeoxyglucose (FDG) PET/CT imaging efficacy in normal ICR, LLC tumor-bearing mice was evaluated. A radiation pneumonia model was then investigated using a gamma counter, small animal PET/CT, and autoradiography. The uptake properties of [F-18]FAPI in lung cancer and acute radiation pneumonia were investigated using autoradiography and PET/CT imaging in mice. Results: The tumor area was visible in [F-18]FAPI imaging and the tracer was swiftly eliminated from normal tissues and organs. There was a significant increase of [F-18]FDG absorption in lung tissue after radiotherapy compared to before radiotherapy, but no significant difference of [F-18]FAPI uptake under the same condition. Furthermore, both the LLC tumor volume and the expression of FAP-alpha decreased after thorax irradiation. Correspondingly, there was no notable [F-18]FAPI uptake after irradiation, but there was an increase of [F-18]FDG uptake in malignancies and lungs. Conclusions: The background uptake of [F-18]FAPI is negligible. Moreover, the uptake of [F-18]FAPI may not be affected by acute radiation pneumonitis compared to [F-18]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.