Usefulness of 18F-FPP-RGD2 PET in pathophysiological evaluation of lung fibrosis using a bleomycin-induced rat model

Purpose Integrins α v are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin α v β 3 imaging for idiopathic pulmonary fibrosis (IPF), we evaluated an 18 F-FPP-RGD 2 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 18 F-FPP-RGD 2 . 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 18 F-FPP-RGD 2 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 18 F-FPP-RGD 2 kinetic analysis in the IPF-model lung. Logan V T values for 18 F-FPP-RGD 2 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 v β 3 PET probe 18 F-FPP-RGD 2 can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin α v of IPF-model rats. These findings support the utility of 18 F-FPP-RGD 2 PET imaging for the pathophysiological evaluation of pulmonary fibrosis.