Zhang Dimei, Shi Yusheng, Kong Jiangwei, Chen Na, Li Guiting, Wang Mingfang, Zhang Guoxia, Zhai Chuangyan
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Department of Radiation Oncology, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 519000, China.
EJNMMI Res. 2024 Jun 18;14(1):57. doi: 10.1186/s13550-024-01118-1.
Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis.
After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUV) was calculated.
PET signals revealed that in areas with evident lesions on CT, the SUV on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUV gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [F]F-FAPI-42 binding to activated fibroblasts.
[F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.
由于治疗选择有限且死亡率高，百草枯（PQ）诱导的肺纤维化带来了重大的医学挑战。因此，迫切需要早期诊断和准确分期以促进适当的治疗策略。在本研究中，我们评估了[F]F-FAPI-42 PET/CT成像在PQ诱导的肺纤维化大鼠模型中早期检测和疾病分期的诊断潜力。
对Sprague-Dawley大鼠口服给予80 mg/kg的PQ后，在给药后第7、14和21天静脉注射3-3.5 MBq的[F]F-FAPI-42。在注射[F]F-FAPI-42后立即进行1小时的动态PET/CT成像。随后，收集肺组织进行苏木精和伊红（HE）染色、Masson三色染色以及NOTA-FAPI-04-MB荧光探针染色。使用Imalytics临床前软件进行数据分析，并计算平均标准化摄取值（SUV）。
PET信号显示，在CT上有明显病变的区域，第14天的SUV显著高于第7天和第21天，表明纤维化活动水平的变化有助于肺纤维化的分期。此外，NOTA-FAPI-04-MB荧光探针染色也显示在第14天探针摄取最为明显。在CT上无明显病变的区域，SUV从第7天到第21天逐渐增加，反映了持续的纤维化活动。此外，HE染色和Masson三色染色未显示肺纤维化，而PET成像能够检测到，达到了早期诊断的目的。在第7、14和21天，PQ组在30分钟和60分钟时的靶本比（TBR）显著高于对照组，表明[F]F-FAPI-42与活化成纤维细胞结合具有高特异性。
[F]F-FAPI-42 PET/CT成像能够对PQ诱导的肺纤维化进行早期诊断和分期，证明了其在表征疾病早期阶段的可行性和潜力。
