USPIOs as targeted contrast agents in cardiovascular magnetic resonance imaging

We aim to discuss the diagnostic use of ultra-small superparamagnetic iron oxide (USPIOs) including ferumoxytol in targeted cardiovascular magnetic resonance imaging (MRI).

Ferumoxytol is the only USPIO clinically available in the U.S. and is a negatively charged USPIO that has potential use for tracking and characterization of macrophage-infiltrated cardiovascular structures. As an iron supplement that is approved for treatment of iron deficiency anemia, the iron core of ferumoxytol is incorporated into the body once it is phagocytosed by macrophages. In organs or tissues with high inflammatory cellular infiltration, such as atherosclerotic plaques and myocardial infarction, localization of iron-laden macrophages can be visualized on delayed MRI. The iron core of ferumoxytol alters the magnetic susceptibility and results in shortening of T2* and T2 relaxation rates. Areas with high concentration appear hypointense (negative contrast) on T2 and T2* MRI. Recently, in vitro findings support the potential specificity of ferumoxytol interactions with macrophage subtypes, which has implications for therapeutic interventions. With increasing concerns about gadolinium retention in the brain and other tissues, the value of ferumoxytol-enhanced MR for targeted clinical imaging is aided by its positive safety profile in patients with impaired renal function.

This paper discusses pharmacokinetic properties of USPIOs with a focus on ferumoxytol, and summarizes relevant in vitro, animal, and human studies investigating the diagnostic use of USPIOs in targeted contrast-enhanced imaging. We also discuss future directions for USPIOs as targeted imaging agents and associated challenges.