Exceedingly small iron oxide nanoparticles as positive MRI contrast agents

Abstract

Significance Gadolinium (Gd)-based contrast agents (GBCAs) are currently the mainstream clinical MRI contrast agents. Some GBCAs have shown a long-term toxicity—nephrogenic systemic fibrosis (NSF)—and Gd depositions in the brain. The NSF has triggered a Food and Drug Administration (FDA) black-box warning and a contraindication of some GBCAs. The finding of Gd depositions led to an ongoing FDA investigation to monitor their possible long-term adverse effects. Here, we present T 1 -weighted contrast-enhanced MR imaging and angiography using zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) in mice and rats. Renal clearance and biodistribution results further demonstrate that ZES-SPIONs are qualitatively different from previously reported SPIONs. This work may open up opportunities to develop exceedingly small SPIONs that show effective T 1 contrast as Gd-free alternatives to GBCAs.