Purpose

Integrins α_v are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin α_vβ₃ imaging for idiopathic pulmonary fibrosis (IPF), we evaluated an ¹⁸F-FPP-RGD₂ PET probe in a rat model of bleomycin-induced lung fibrosis.

Methods

Pulmonary fibrosis was induced by single intratracheal instillation of bleomycin (3 mg/rat). Positron emission tomography (PET)/computerized tomography scans were performed 4 weeks after bleomycin administration using ¹⁸F-FPP-RGD₂. Total distribution volume (V_T) was estimated using one-tissue/two-compartment, two-tissue/three-compartment models, and Logan graphical analysis (Logan plot; t* = 30 min). Plasma-free fractions were estimated from images of the left ventricle. Correlation between Logan V_T and lung pathology was assessed by Spearman’s rank correlation.

Results

Histopathological evaluation demonstrated the development of fibrosis in IPF-model group. Integrin α_v protein expression and lung radioactivity were higher in IPF-model group compared with control group. The lung radioactivity of ¹⁸F-FPP-RGD₂ rapidly reached the peak after administration and then gradually decreased, whereas left ventricular radioactivity rapidly disappeared. Logan graphical analysis was found to be suitable for ¹⁸F-FPP-RGD₂ kinetic analysis in the IPF-model lung. Logan V_T values for ¹⁸F-FPP-RGD₂ were significantly higher in IPF rats compared with control rats and strongly correlated with lung fibrosis, pathology, integrin α_v protein expression, and oxygen partial pressure.

Conclusion

Our findings demonstrate that the integrin α_vβ₃ PET probe ¹⁸F-FPP-RGD₂ can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin α_v of IPF-model rats. These findings support the utility of ¹⁸F-FPP-RGD₂ PET imaging for the pathophysiological evaluation of pulmonary fibrosis.

中文翻译：

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18F-FPP-RGD2 PET 在使用博来霉素诱导的大鼠模型肺纤维化的病理生理学评估中的有用性

目的

整合素αv是多器官纤维化发病机制中的关键分子_。为了评估整合素 α _v β ₃成像对特发性肺纤维化 (IPF) 的潜在效用，我们在博来霉素诱导的肺纤维化大鼠模型中评估了¹⁸ F-FPP-RGD _{2 PET 探针。}

方法

肺纤维化是通过单次气管内滴注博来霉素（3 毫克/大鼠）诱导的。^使用18 F-FPP-RGD ₂在施用博来霉素后4周进行正电子发射断层扫描(PET)/计算机断层扫描。使用单组织/双隔室、双组织/三隔室模型和洛根图分析（洛根图；t* = 30 分钟）估算总分布容积 ( V _{T )。}从左心室的图像估计无血浆部分。Logan VT与肺_病理学之间的相关性通过 Spearman 等级相关性进行评估。

结果

组织病理学评估证明了 IPF 模型组中纤维化的发展。与对照组相比，IPF模型组整合素αv蛋白表达_{和肺放射性更高。}¹⁸ F-FPP-RGD ₂给药后肺部放射性迅速达到峰值后逐渐下降，而左心室放射性迅速消失。发现洛根图形分析适用于IPF 模型肺中的¹⁸ F-FPP-RGD _{2动力学分析。}¹⁸ F-FPP-RGD ₂的Logan V _T值与对照大鼠相比，IPF 大鼠的显着更高，并且与肺纤维化、病理学、整合素 α _v蛋白表达和氧分压密切相关。

结论

我们的研究结果表明，整合素 α _v β ₃ PET 探针¹⁸ F-FPP-RGD ₂可以检测肺部的病理生理变化，包括伴随IPF 模型大鼠上调的整合素 α _{v的纤维化。}这些发现支持¹⁸ F-FPP-RGD ₂ PET 成像用于肺纤维化的病理生理学评估的效用。