Mapping Fibroblast Activation in Atherosclerosis and Valvular Disease Using ⁶⁸Ga-FAPI-46 PET/CT

Ziel/Aim: Imaging fibroblast activation enables the identification of fibrotic and remodeling-associated processes in atherosclerotic plaques and cardiac valves. This study aimed to characterize vascular wall– and valve-associated ⁶⁸Ga-FAPI-46 uptake patterns and their relationships with morphological calcifications, cardiovascular risk factors and laboratory values. Methodik/Methods: 70 patients with cardiovascular disease (44 with acute myocardial infarction [AMI], 26 with severe aortic stenosis [AS]) underwent ⁶⁸Ga-FAPI-46 PET/CT (121±23 MBq; 60 min p.i.). Quantitative analysis of PET-positive plaques in thoracic and abdominal aortic walls (SUVmax, target-to-background ratio [TBR]), of the aortic and mitral valves, and a CT-based analysis of calcified lesions was performed. Ergebnisse/Results: Focal FAPI uptake was detected at 639 sites in 100% of patients (mean SUVmax=2.8±0.6; TBR=1.6±0.3; mean 9.1±1.8 lesions per patient, range 6-14 lesions per patient). Calcified lesions were present at 676 sites in 93% of patients (mean thickness=3.0±0.1 mm). On a lesion level, 266/676 (39%) PET-positive lesions exhibited colocalized calcification. Mean SU-Vmax was 3.4±0.9 in the aortic vessel wall and 2.8±0.7 in the mitral valve. SUVmax in PET-positive aortic plaques correlated with maximum plaque diameter (r=0.342; p=0.004), aortic valve SUVmax (r=0.282; p=0.018), mitral valve SUVmax (r=0.501; p<0.001), presence of diabetes mellitus (r=0.388; p=0.001) or obesity (r=0.481; p<0.001) and C-reactive protein levels (r=0.253; p=0.039). While the number of PET-positive plaques was similar between AS and AMI (p=0.079), AS patients had significantly more CT-positive plaques (mean 15.2±5.3 vs. 6.4±4.8; p<0.001) and PET and CT positive lesions (colocalization sites; mean 5.5±2.5 vs. 2.8±2.0; p<0.001). Schlussfolgerungen/Conclusion: ⁶⁸Ga-FAPI-46 PET reveals widespread fibroblast activation in vascular and valvular structures of cardiovascular patients, correlating with calcification burden, comorbidities and inflammatory laboratory values. These findings suggest that FAPI imaging may serve as a marker of active tissue remodeling in vessel walls and valves beyond established calcific disease in patients with existing cardiovascular disease. Publication History Article published online: 02 April 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany