Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT
Christoph Treutlein, Jörg H. W. Distler, Koray Taşçılar, Sara Chenguiti Fakhouri, Andrea‐Hermina Györfi, Armin Atzinger, Alexandru‐Emil Matei, Clara Dees, Maike Büttner‐Herold, Torsten Kuwert, Olaf Prante, Tobias Bäuerle, Michael Uder, Georg Schett, Christian Schmidkonz, Christina Bergmann
Abstract
Abstract Purpose Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68 Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([ 68 Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF. Methods In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [ 68 Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated. Results [ 68 Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [ 68 Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP + fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [ 68 Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [ 68 Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [ 68 Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage. Conclusions We present first in-human evidence that [ 68 Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.