Fibroblast activation protein imaging in atrial fibrillation: a proof-of-concept study

Abstract Purpose: Radiolabeled fibroblast activation protein inhibitor (FAPI) imaging has proven feasible in the assessment of ventricular fibrosis in several cardiovascular diseases. However, its value in assessing atrial fibrosis in atrial fibrillation (AF) remains unknown. Methods: Twenty-eight patients with AF and 25 sex-matched controls underwent baseline FAPI PET/CT imaging. Left atrial appendage (LAA) specimens were obtained from seven patients and two lung transplant donors. Atrial pacing beagle dog AF models were constructed by pacemaker implantation. After 8 weeks of pacing, the animals underwent FAPI PET/CT imaging and specimens from the left atrial and right atrial (LA, RA) were collected. FAPI activities in the LA, RA, and LAA were measured by target-to-background ratio (TBR), and the mRNA and protein expression of fibroblast activation protein (FAP) and collagen I were measured by quantitative polymerase chain reaction (PCR) and western blot. Results: FAPI imaging identified increased atrial uptake in 17 patients with persistent AF (PsAF) (85.00%) and 5 with paroxysmal AF (PAF) (62.50%), located in the LA (64.28%), RA (57.14%), and LAA (42.86%). In all atrial structures, patients with PsAF had a higher prevalence of enhanced FAPI uptake than those with PAF (63.33% vs. 33.33%, P = 0.02). LA dilation and B-type natriuretic peptide level were determined as independent factors for increased LAA and RA FAPI uptake, respectively (OR: 1.11 and 1.02, both P < 0.05). All five beagles with AF had increased FAPI uptake in the LA and RA. For both human and animal specimens, FAPI activity was strongly associated with the mRNA and protein levels of FAP, and was closely related to the mRNA expression of collagen I. Conclusion: This preliminary study suggests that FAPI imaging is feasible for assessing activated fibroblasts in the atriums of AF.