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

Objective: In this study, the uptake characteristics of [F]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]FAPI positron emission tomography/computed tomography (PET/CT) imaging in early radiotherapy response. Methods: Initially, the biodistribution of [F]FAPI tracer in vivo were studied in healthy mice at each time-point. A comparison of [F]FAPI and [F]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]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]FAPI imaging and the tracer was swiftly eliminated from normal tissues and organs. There was a significant increase of [F]FDG absorption in lung tissue after radiotherapy compared to before radiotherapy, but no significant difference of [F]FAPI uptake under the same condition. Furthermore, both the LLC tumor volume and the expression of FAP-ɑ decreased after thorax irradiation. Correspondingly, there was no notable [F]FAPI uptake after irradiation, but there was an increase of [F]FDG uptake in malignancies and lungs. Conclusions: The background uptake of [F]FAPI is negligible. Moreover, the uptake of [F]FAPI may not be affected by acute radiation pneumonitis compared to [F]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.