| First Author | Schniering J | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 2724 | PubMed ID | 31824505 |
| Mgi Jnum | J:297955 | Mgi Id | MGI:6479447 |
| Doi | 10.3389/fimmu.2019.02724 | Citation | Schniering J, et al. (2019) (18)F-AzaFol for Detection of Folate Receptor-beta Positive Macrophages in Experimental Interstitial Lung Disease-A Proof-of-Concept Study. Front Immunol 10:2724 |
| abstractText | Background: Interstitial lung disease (ILD) is a common and severe complication in rheumatic diseases. Folate receptor-beta is expressed on activated, but not resting macrophages which play a key role in dysregulated tissue repair including ILD. We therefore aimed to pre-clinically evaluate the potential of (18)F-AzaFol-based PET/CT (positron emission computed tomography/computed tomography) for the specific detection of macrophage-driven pathophysiologic processes in experimental ILD. Methods: The pulmonary expression of folate receptor-beta was analyzed in patients with different subtypes of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. PET/CT was performed at days 3, 7, and 14 after BLM instillation using the (18)F-based folate radiotracer (18)F-AzaFol. The specific pulmonary accumulation of the radiotracer was assessed by ex vivo PET/CT scans and quantified by ex vivo biodistribution studies. Results: Folate receptor-beta expression was 3- to 4-fold increased in patients with fibrotic ILD, including idiopathic pulmonary fibrosis and connective tissue disease-related ILD, and significantly correlated with the degree of lung remodeling. A similar increase in the expression of folate receptor-beta was observed in experimental lung fibrosis, where it also correlated with disease extent. In the mouse model of BLM-induced ILD, pulmonary accumulation of (18)F-AzaFol reflected macrophage-related disease development with good correlation of folate receptor-beta positivity with radiotracer uptake. In the ex vivo imaging and biodistribution studies, the maximum lung accumulation was observed at day 7 with a mean accumulation of 1.01 +/- 0.30% injected activity/lung in BLM-treated vs. control animals (0.31 +/- 0.06% % injected activity/lung; p < 0.01). Conclusion: Our preclinical proof-of-concept study demonstrated the potential of (18)F-AzaFol as a novel imaging tool for the visualization of macrophage-driven fibrotic lung diseases. |
