Intracoronary injection of the bone marrow-derived mononuclear cells (MNCs) is emerging as a potentially novel therapy for ischemic heart failure. This study was aimed at assessing the efficacy of intracoronary MNC delivery in the myocardium. The in vivo distribution and myocardial homing of intracoronarily delivered MNCs in experimental Chinese swine with acute myocardial infarction (AMI) created by occlusion of left anterior descending (LAD) coronary artery for 90 min. MNCs radiolabeled with 18F-fluoro-deoxy-glucose (18F-FDG) were delivered using a coronary catheter into the infarct-related coronary artery 1 week after AMI. Dual-nuclide single photon emission computed tomography (SPECT) revealed that 1 h after cell infusion, 6.8 +/- 1.8% of 18F-FDG-labeled MNCs occurred in the infarcted myocardium with the remaining activity found primarily in the liver and spleen. In the heart, MNCs were detected predominantly in the under-perfused myocardium. The infused cells retained in the hearts at a rate highly correlated with the under-perfused lesional sizes. Pathological examination further demonstrated that 6 weeks after infusion, compared to controls, the hearts receiving MNCs exhibited less fibrosis and inflammatory infiltrate, more viable tissue, and higher vascular density. Cardiac function was significantly improved in the MNC-infused hearts. Thus, 18F-FDG labeling and dual-nuclide SPECT imaging is capable of monitoring in vivo distribution and homing of MNCs after intracoronary infusion. MNC coronary delivery may improve cardiac function and positive ventricular remodeling in the heart with AMI.