Nanoparticulate Iron Oxide Contrast Agents for Untargeted and Targeted Cardiovascular Magnetic Resonance Imaging

In cardiology and oncology, early disease detection produces better patient outcomes. Imaging approaches, particularly Mag- netic Resonance Imaging (MRI), are attractive for screening large, mostly disease-free populations because they are noninvasive and pro- duce high-resolution anatomical/morphological images from disease sites. Biochemically targeted nanoparticulate contrast agents (ul- trasmall superparamagnetic iron oxide particles called USPIOs, superparamagnetic iron oxide nanoparticles called SPIONs, cross-linked iron oxides called CLIOs, Gadolinium chelates, and other superparamagnetic or paramagnetic particles) can be administered parenterally to define lesional biochemical/cellular composition, in addition to giving excellent definition of morphological features. Such targeted contrast agents can be considered modular nanobiological devices containing, at minimum, a contrast module and a targeting moiety. Here we review synthesis, surface chemistry and physics of superparamagnetic iron oxide MRI contrast agents (USPIOs and SPIONs) and results to date from the use of biochemically targeted and untargeted iron oxide MRI contrast agents in vivo, in vitro and ex vivo in vascular disease, and to a lesser extent, in oncology applications. We discuss design parameters critical to in vivo use of targeted contrast particles, including parameters influencing particle biodistribution/pharmacokinetics and immunogenicity. We discuss the increasing so- phistication of theranostic contrast agents that provide other physiological services concurrent with their MRI function.