Abstract 12181: Targeted Intra-Coronary Delivery versus Intra-Myocardial Injection of Therapeutics for Myocardial Recovery: A Nanoparticle Image Guided Porcine Study

Abstract

Introduction: The optimal cardiac delivery route for stem cell and gene therapeutics is poorly understood. Direct intramyocardial (IM) injection has been proposed as the gold standard, however, it is invasive and not studied in detail against targeted intra-coronary (IC) delivery techniques. We sought to compare effectiveness of IM and targeted IC methods using cardiac magnetic resonance imaging (CMR) of nanoparticles in a porcine model. Hypothesis: IM provides the highest retention of delivered therapeutic, while targeted IC delivery yields high-volume retention in the perfused coronary territory. Methods: In Yorkshire swine (n=10), 5ml of ferumoxytol iron oxide (IO) nanoparticles, similar in size to therapeutic viral vectors, were injected: 1) IM via thoracotomy (n=3), 2) catheter based IC balloon-occlusion (BO) with distal infusion of the LAD (n=4), 3) IC with perforated balloon side wall (SW) infusion in the LAD (n=2), or 4) IC non-selective left main (LM) (n=1). Hearts were harvested and imaged with CMR using T1 and 3D inversion-recovery sequences. Retention of nanoparticles was quantified by percent of myocardium occupied. Results: IM delivery yielded the highest retention (16.3±5.5% of myocardial volume, p=0.04). Of the IC approaches, BO had the highest retention (8.7±2.2%, p=0.13 vs IM) compared to SW (5.5±4.9%) and LM (0%). On 3D CMR, BO yielded consistent uptake in the distal LAD territory, including the anterior wall and septum. IM delivery was limited to the anterior wall with no nanoparticles in the septum. Troponin increased 15,600±4,910 with IM vs.184±262 with IC (p=0.14). Conclusions: Direct IM injection offers the highest retention of delivered therapeutics to the heart. IC balloon occlusion-distal infusion has highest retention among IC techniques and provides an effective approach to direct therapeutics to the vascular bed most impacted by an infarct.