Molecular magnetic resonance imaging with microparticles of iron oxide. (360G-Wellcome-088291_Z_09_Z)

We have designed, developed and applied a new class of molecular magnetic resonance imaging agent. Ligand-conjugated iron oxide microparticles (MPIO). For the majority of contrast agent approaches there has been no attempt to apply the agent in the very roles for which they were developed. However, for MPIO, where contrast effects are highly conspicuous and readily quantifiable, there is a compelling case to proceed to a more sophisticated assessment of utility. Therefore, in Aim 1 we will tes t MPIO in three critical areas: (A) Non-invasive quantification of molecular expression and distribution with corroboration through tissue analyses. (B) Identification of pre-lesion molecular signals that anticipate the later development of atherosclerosis. (C) Monitoring responses to treatment that are not apparent using conventional anatomical imaging techniques. Aim 2 will focus on refinements in targeting strategies and MPIO design to make more biologically effective contrast agents. We will test association / dissociation kinetics and affinities of MPIO conjugated to a range of ligands (including novel synthetic glycoproteins) under flow conditions in vitro and we will evaluate the properties of a new class of biodegradable MPIO in vitro and in vivo, including disposal and dispersal if the iron oxide core.