Diagnostic Value of 18 F-NOTA-FAPI PET/CT in A Rat Model of Radiation-induced Lung Damage

Background: In this study, we explore the diagnostic value of a novel PET/CT imaging tracer that specifically targets fibroblast activation protein (FAP), 18 F-NOTA-FAPI, in a radiation induced lung damage (RILD) rat model. Methods: : High focal radiation (40, 60, or 90 Gy) was administered to a 5-mm diameter area of the right lung in Wistar rats for evaluation of RILD induction. Lung tissues exposed to 90 Gy radiation were scanned with 18 F-NOTA-FAPI PET/CT and with 18 F- FDG. Dynamic 18 F-NOTA-FAPI PET scanning was performed on day 42 post-irradiation. After in vivo scanning, lung cryosections were prepared for autoradiography, hematoxylin and eosin (HE) and immunohistochemical (IHC) staining. Results: : An animal model of RILD was established and validated by histopathological analysis. On 18 F-NOTA-FAPI PET, RILD was first observed on days 42, 35 and 7 in the 40, 60 and 90 Gy groups, respectively. After treatment with 90 Gy, 18 F-NOTA-FAPI uptake in an area of RILD emerged on day 7 (0.65±0.05 %ID/ml) and reappeared on day 28 (0.81±0.09 %ID/ml), remaining stable for 4–6 weeks. Autoradiography and HE staining IHC staining revealed that 18 F-NOTA-FAPI accumulated mainly in the center of the irradiated area. IHC staining confirmed the presence of FAP+ macrophages in the RILD area, while FAP+ fibroblasts were observed in the peripheral area of irradiated lung tissue. Conclusion: 18 F-NOTA-FAPI represents a promising radiotracer for in vivo imaging of RILD in a dose- and time-dependent manner. Noninvasive imaging of FAP may potentially aiding in the clinical management of radiotherapy patients.