Assessment of myocardial fibrosis in patients with systemic sclerosis using [⁶⁸Ga]Ga-FAPI-04-PET-CT

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 ⁶⁸Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([⁶⁸Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF.

In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [⁶⁸Ga]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.

[⁶⁸Ga]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 [⁶⁸Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP⁺ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [⁶⁸Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [⁶⁸Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [⁶⁸Ga]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.

We present first in-human evidence that [⁶⁸Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.