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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 13/2022

25-07-2022 | Idiopathic Pulmonary Fibrosis | Original Article

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

Authors: Shuichi Hiroyama, Keiko Matsunaga, Miwa Ito, Hitoshi Iimori, Minako Tajiri, Yoshiyuki Nakano, Eku Shimosegawa, Kohji Abe

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 13/2022

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Abstract

Purpose

Integrins αv are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin αvβ3 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 (VT) 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 VT and lung pathology was assessed by Spearman’s rank correlation.

Results

Histopathological evaluation demonstrated the development of fibrosis in IPF-model group. Integrin αv 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 VT values for 18F-FPP-RGD2 were significantly higher in IPF rats compared with control rats and strongly correlated with lung fibrosis, pathology, integrin αv protein expression, and oxygen partial pressure.

Conclusion

Our findings demonstrate that the integrin αvβ3 PET probe 18F-FPP-RGD2 can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin αv of IPF-model rats. These findings support the utility of 18F-FPP-RGD2 PET imaging for the pathophysiological evaluation of pulmonary fibrosis.
Appendix
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Metadata
Title
Usefulness of 18F-FPP-RGD2 PET in pathophysiological evaluation of lung fibrosis using a bleomycin-induced rat model
Authors
Shuichi Hiroyama
Keiko Matsunaga
Miwa Ito
Hitoshi Iimori
Minako Tajiri
Yoshiyuki Nakano
Eku Shimosegawa
Kohji Abe
Publication date
25-07-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 13/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05908-4

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