In:
European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 50, No. 6 ( 2023-05), p. 1629-1635
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1619-7070
,
1619-7089
DOI:
10.1007/s00259-022-06081-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2098375-X