USPIO-loaded red blood cells as a biomimetic MR contrast agent: a relaxometric study

Red blood cells (RBCs) loaded with iron oxide nanoparticles have been proposed as biomimetic constructs with long half-life (ca. 20days) in the blood compartment and potentially interesting properties (such as relaxivity) as intravascular contrast agents for magnetic resonance imaging. However, the encapsulation of nanoparticles into RBCs might affect their magnetic properties and relaxivity, which may be significantly different from the native suspension. Here, we present a relaxometric study of P904, a novel ultra small iron oxide nanoparticle developed by Guerbet, enclosed in human RBCs. We measured longitudinal (r(1)) and transverse (r(2)) relaxivity over a wide range of Larmor frequencies (0.01-300MHz) in samples of P904-loaded RBCs, and in control samples with P904 nanoparticles dispersed in blood. Internalization of P904 into RBCs resulted in smaller r(1), and in a very high r(2)/r(1) ratio (232) at the highest field. Moreover, a shift of the Curie peak to high fields was observed in P904-loaded RBCs, possibly the result of nanoparticle size selection caused by the internalization process. High r(2) relaxivity together with a high r(2)/r(1) ratio and a very long blood half-life make P904-loaded RBCs a promising blood-pool negative contrast agent for MR diagnostic applications. Copyright (c) 2014 John Wiley & Sons, Ltd.