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

Abstract

Background: To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of individuals with AF and to identify factors contributing to enhanced atrial activity.

Methods: We constructed left atrial appendage (LAA) pacing beagle dog AF models (n = 5) and conducted ¹⁸F-FAPI PET/CT imaging at baseline and eight weeks after pacing. Right atrial (RA) specimens were collected from these models. Additionally, 28 AF patients and ten age- and sex-matched healthy volunteers underwent ¹⁸F-FAPI PET/CT imaging.

Results: RA of AF beagles showed increased ¹⁸F-FAPI uptake. Among AF patients, 18 out of 28 (64.3%) exhibited enhanced atrial FAPI activity. No atrial ¹⁸F-FAPI uptake was observed in the sham beagle and healthy volunteers. In animal RA specimens, ¹⁸F-FAPI activity correlated positively with FAP mRNA (r = .98, P = .002) and protein (r = .82, P = .03) levels, as well as collagen I mRNA expression (r = .85, P = .02). B-type natriuretic peptide levels were associated with atrial ¹⁸F-FAPI activity (OR = 3.01, P = .046).

Conclusion: This proof-of-concept study suggests that ¹⁸F-FAPI PET/CT imaging may be a feasible method for evaluating activated fibroblasts in the atria of AF patients.

Keywords: 18F-FAPI; Atrial fibrillation; PET/CT; fibrosis.