Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease. However, the definitive diagnosis of IPF is impeded by the limited capabilities of current diagnostic methods, which may fail to capture the optimal timing for treatment. The main goal of this study is to determine the feasibility of a nitroreductase (NTR) responsive probe, F-NCRP, for early detection and deterioration monitoring of IPF. F-NCRP was obtained with high radiochemical purity (>95 %). BLM-injured mice were established by intratracheal instillation with bleomycin (BLM) and characterized through histological analysis. Longitudinal PET/CT imaging, biodistribution study and autoradiography were performed. The correlations between the uptake of F-NCRP and mean lung density (tested by CT), as well as histopathological characteristics were analyzed. In PET imaging study, F-NCRP exhibited promising efficacy in monitoring the progression of IPF, which was earlier than CT. The ratio of uptake in BLM-injured lung to control lung increased from 1.4-fold on D15 to 2.2-fold on D22. Biodistribution data showed a significant lung uptake of F-NCRP in BLM-injured mice. There was a strong positive correlation between the F-NCRP uptake in the BLM-injured lungs and the histopathological characteristics. Given that, F-NCRP PET imaging of NTR, a promising biomarker for investigating the underlying pathogenic mechanism of IPF, is attainable as well as desirable, which might lay the foundation for establishing an NTR-targeted imaging evaluation system of IPF.

中文翻译：

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用于肺纤维化疾病早期诊断的硝基还原酶响应探针


特发性肺纤维化（IPF）是一种严重的间质性肺疾病。然而，当前诊断方法的能力有限，阻碍了 IPF 的明确诊断，可能无法捕捉到最佳治疗时机。本研究的主要目标是确定硝基还原酶 (NTR) 响应探针 F-NCRP 用于 IPF 早期检测和恶化监测的可行性。获得的 F-NCRP 具有高放射化学纯度 (>95 %)。通过气管内滴注博莱霉素（BLM）建立 BLM 损伤小鼠，并通过组织学分析进行表征。进行了纵向 PET/CT 成像、生物分布研究和放射自显影。分析F-NCRP的摄取与平均肺密度（通过CT检测）以及组织病理学特征之间的相关性。在PET成像研究中，F-NCRP在监测IPF进展方面表现出良好的效果，且比CT更早。 BLM损伤肺与对照肺的摄取比率从第15天的1.4倍增加到第22天的2.2倍。生物分布数据显示 BLM 损伤小鼠肺部显着摄取 F-NCRP。 BLM损伤肺部的F-NCRP摄取与组织病理学特征之间存在很强的正相关性。鉴于此，NTR的F-NCRP PET成像是研究IPF潜在致病机制的一种有前景的生物标志物，是可以实现的，也是理想的，这可能为建立针对IPF的NTR靶向成像评估系统奠定基础。