Qin Xueting, Wang Shijie, Liu Xiaoli, Duan Jinghao, Cheng Kai, Mu Zhengshuai, Jia Jing, Wei Yuchun, Yuan Shuanghu
Department of Radiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Oncol. 2022 Jun 2;12:879281. doi: 10.3389/fonc.2022.879281. eCollection 2022.
In this study, we explore the diagnostic value of a novel PET/CT imaging tracer that specifically targets fibroblast activation protein (FAP), F-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 F-NOTA-FAPI PET/CT and with F-FDG. Dynamic F-NOTA-FAPI PET/CT scanning was performed on day 42 post-irradiation. After 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 F-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, 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 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. F-NOTA-FAPI represents a promising radiotracer for imaging of RILD in a dose- and time-dependent manner. Noninvasive imaging of FAP may potentially aiding in the clinical management of radiotherapy patients.
在本研究中,我们在放射性肺损伤(RILD)大鼠模型中探索了一种新型PET/CT成像示踪剂F-NOTA-FAPI的诊断价值,该示踪剂特异性靶向成纤维细胞活化蛋白(FAP)。对Wistar大鼠右肺直径5毫米的区域给予高剂量局部辐射(40、60或90 Gy),以评估RILD的诱导情况。对接受90 Gy辐射的肺组织进行F-NOTA-FAPI PET/CT和F-FDG扫描。在照射后第42天进行动态F-NOTA-FAPI PET/CT扫描。扫描后,制备肺冰冻切片用于放射自显影、苏木精和伊红(HE)染色以及免疫组织化学(IHC)染色。通过组织病理学分析建立并验证了RILD动物模型。在F-NOTA-FAPI PET/CT上,40、60和90 Gy组分别在第42天、35天和7天首次观察到RILD。给予90 Gy治疗后,RILD区域的F-NOTA-FAPI摄取在第7天出现(0.65±0.05%ID/ml),并在第28天再次出现(0.81±0.09%ID/ml),持续稳定4 - 6周。放射自显影和HE染色的IHC染色显示,F-NOTA-FAPI主要聚集在照射区域的中心。IHC染色证实RILD区域存在FAP+巨噬细胞,而在照射肺组织的周边区域观察到FAP+成纤维细胞。F-NOTA-FAPI是一种有前景的放射性示踪剂,可用于以剂量和时间依赖性方式对RILD进行成像。FAP的无创成像可能有助于放疗患者的临床管理。