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

Abstract

In this study, we explore the diagnostic value of a novel PET/CT imaging tracer that specifically targets fibroblast activation protein (FAP), 18F-NOTA-FAPI, in a radiation induced lung damage (RILD) rat model. 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 18F-NOTA-FAPI PET/CT and with 18F-FDG. Dynamic 18F-NOTA-FAPI PET/CT 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. An animal model of RILD was established and validated by histopathological analysis. On 18F-NOTA-FAPI PET/CT, RILD was first observed on days 42, 35 and 7 in the 40, 60 and 90 Gy groups, respectively. After treatment with 90 Gy, 18F-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 18F-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. 18F-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.

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

“…Qin et al [ 10 ] monitored the development of lung tissue damage after radiotherapy and determined the uptake of [ 18 F]FAPI in the stage of pulmonary fibrosis in a rat model, which is consistent with the results of previous studies. However, no studies have focused on the acute inflammatory stage.…”

“…Fibroblasts are persistently activated in chronic fibrosis and tumor fibrosis, but not in acute inflammation [ 9 ]. In the study by Qin et al [ 10 ], [ 18 F]FAPI uptake was observed on day 7 in the 90 Gy group with foamy macrophages and slight collagen deposition present which should be classified as chronic inflammatory phase. The reason for the inconsistency with our results may be the difference in radiation dose and the radiosensitivity of different murine.…”

Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

“…Although there have been no systematic reports of FAP expression in granulomas, granulomatous lesions may show high FAP expression. Regarding radiation pneumonitis, Qin et al reported increased FAP expression and FAPI uptake in a rat model of radiation-induced lung damage (20). Further, R€ ohrich et al reported increased uptake in fibrotic lung disease (21).…”

“…Regarding radiation pneumonitis, Qin et al. reported increased FAP expression and FAPI uptake in a rat model of radiation-induced lung damage ( 20 ). Further, Röhrich et al.…”

Recent Advances in Cardiovascular Diseases Research Using Animal Models and PET Radioisotope Tracers

“…For example, for longer FAP tracking 18 F-based radiotracers are considered to be more preferable compared to the 68 Ga-based ones [136]. The recently developed fluorine-18-based markers targeting FAP have been tested in the rat model of radiation-induced lung damage [190] and in tumour uptake models [191,192], including the mice model of breast cancer [193].…”