Radiolabeled GPVI-Fc for PET imaging of multiple extracellular matrix fibers: A new look into pulmonary fibrosis progression.

Invariably fatal and with a particularly fast progression, pulmonary fibrosis (PF) is currently devoid of curative treatment option. Routine clinical diagnosis relies on breathing tests and visualizing the changes in lung structure by computed tomography (CT), but anatomical information is often not sufficient to identify early signs of progressive PF. For more efficient diagnosis, additional imaging techniques were investigated in combination with CT, such as 18 F-Fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET), although with limited success due to lack of disease specificity. Therefore, novel molecular targets enabling specific diagnosis are investigated, in particular for molecular imaging techniques. Methods: In this study, we used a 64 Cu-radiolabelled platelet glycoprotein VI fusion protein (64 Cu-GPVI-Fc), targeting extracellular matrix fibers (ECM) as a PET tracer to observe longitudinally ECM remodeling in a bleomycin-induced PF mouse model. Results: 64 Cu-GPVI-Fc showed a significant uptake in fibrotic lungs, matching histology results. Contrary to 18 F-FDG PET measurements, 64 Cu-GPVI-Fc uptake was entirely linked to the fibrotic activity of tissue and not susceptible to inflammation. Conclusion: Our study highlights 64 Cu-GPVI-Fc as a specific tracer for ECM remodeling in PF, with a clear therapy monitoring and clinical translation potential.