Preclinical Evaluation ofCu-LNTH-1363S to Detect Cardiac FAP-Positive Fibroblasts Using PET Imaging.

Abstract

Fibroblast activation protein-expressing (FAP+) fibroblasts are central mediators of cardiac remodeling after injury or disease. The aim of this study was to evaluate a new PET tracer,Cu-LNTH-1363S, to detect FAP+ fibroblasts in myocardial infarction (MI) mouse models.The permanent left anterior descending coronary artery ligation and the echocardiography-guided ischemia reperfusion models were used to assess the targeting efficiency ofCu-LNTH-1363S. Competitive receptor blocking and autoradiography studies were performed to confirm the in vivo targeting specificity.Cu-LNTH-1363S demonstrated sensitive and specific detection of FAP+ cells in the 2 MI models. Kinetic modeling data showed that the distribution volume was higher in the infarct zone than in the remote myocardium.This study establishes the feasibility ofCu-LNTH-1363S for noninvasive detection of FAP+ fibroblasts in MI mouse models and provides preclinical data to support further investigation of this process in humans after various forms of cardiac injury.