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

Purpose: Integrins α are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin αβ imaging for idiopathic pulmonary fibrosis (IPF), we evaluated an F-FPP-RGD 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 F-FPP-RGD. Total distribution volume (V) 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 and lung pathology was assessed by Spearman's rank correlation.

Results: Histopathological evaluation demonstrated the development of fibrosis in IPF-model group. Integrin α protein expression and lung radioactivity were higher in IPF-model group compared with control group. The lung radioactivity of F-FPP-RGD 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 F-FPP-RGD kinetic analysis in the IPF-model lung. Logan V values for F-FPP-RGD were significantly higher in IPF rats compared with control rats and strongly correlated with lung fibrosis, pathology, integrin α protein expression, and oxygen partial pressure.

Conclusion: Our findings demonstrate that the integrin αβ PET probe F-FPP-RGD can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin α of IPF-model rats. These findings support the utility of F-FPP-RGD PET imaging for the pathophysiological evaluation of pulmonary fibrosis.