Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging

Schmidkonz C, Rauber S, Atzinger A, Götz TI, Soare A, Cordes M, Prante O, Ritt P, Bäuerle T, Köhner M, Haberkorn U, Kuwert T, Schett G, Ramming A (2021)

Publication Type: Journal article

Publication year: 2021


Publisher: SPRINGER

City/Town: NEW YORK

Pages Range: S125-S126


DOI: 10.1055/s-0041-1726701


Ziel/Aim To date, there is no valuable tool to assess fibrotic disease activity in humans in vivo in a non-invasive way. This study aims to uncouple inflammatory from fibrotic disease activity in fibroinflammatory diseases such as IgG4-related disease.

Methodik/Methods In this cross-sectional clinical study, 27 patients with inflammatory, fibrotic and overlapping manifestations of IgG4-related disease underwent positron emission tomography (PET) scanning with tracers specific for fibroblast activation protein (FAP; 68Ga-FAP inhibitor (FAPI)-04), 18F-fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI) and histopathological assessment. In a longitudinal approach, 18F-FDG and 68Ga-FAPI-04 PET/CT data were evaluated before and after immunosuppressive treatment and correlated to clinical and MRI data.

Ergebnisse/Results Using combination of 68Ga-FAPI-04 and 18F-FDG-PET, we demonstrate that non-invasive functional tracking of IgG4-related disease evolution from inflammatory towards a fibrotic outcome becomes feasible. 18F-FDG-PET positive lesions showed dense lymphoplasmacytic infiltration of IgG4 + cells in histology, while 68Ga-FAPI-04 PET positive lesions showed abundant activated fibroblasts expressing FAP according to results from RNA-sequencing of activated fibroblasts. The responsiveness of fibrotic lesions to anti-inflammatory treatment was far less pronounced than that of inflammatory lesions.

Schlussfolgerungen/Conclusions FAP-specific PET/CT permits the discrimination between inflammatory and fibrotic activity in IgG4-related disease. This finding may profoundly change the management of certain forms of immune-mediated disease, such as IgG4-related disease, as subtypes dominated by fibrosis may require different approaches to control disease progression, for example, specific antifibrotic agents rather than broad spectrum anti-inflammatory treatments such as glucocorticoids.

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Schmidkonz, C., Rauber, S., Atzinger, A., Götz, T.I., Soare, A., Cordes, M.,... Ramming, A. (2021). Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging. European Journal of Nuclear Medicine and Molecular Imaging, S125-S126. https://doi.org/10.1055/s-0041-1726701


Schmidkonz, Christian, et al. "Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging." European Journal of Nuclear Medicine and Molecular Imaging (2021): S125-S126.

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