Twelve superparamagnetic Magnetite-Dextran (MD) nanoparticles potentially useful as contrast agents for Magnetic Resonance Imaging (MRI), with different sizes, charges and surface natures, were produced and internally labelled with (59)Fe in order to investigate the effect of their physicochemical properties on their biodistribution in mice. In a first step, neutral MD particles of a size 33-90.6 nm were studied. Next, the influence of charge was investigated with negative and positive particles (MDL, MDD, MDDEAE). The former (-25, -30 mV) were small, around 30 nm in size whereas the latter (+20 mV) were larger (104 nm). The effect of surface nature was evaluated using MD particles coated with polyoxyethylene-polyoxypropylene copolymers (Synperonic: these MDP particles were neutral and larger in size (65.9-76.4 nm). Experiments showed that 20 min post-injection (2 mg Fe/kg), liver uptake was enhanced when the mean diameter increased: 22% for the smallest and 42% for the largest. It was up to 3 X lower for electrically neutral particles than for charged particles. Coated particles presented higher vascular persistence. The diagnostic potential for liver, lymph node or vascular imaging were discussed.

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Relations between spatial distribution of superparamagnetic iron oxide (SPIO) particles and the image contrast caused by SPIO were investigated. Actual clustering pattern of particles was measured in the liver and spleen of animals using intravital laser confocal microscopy. SPIOdoped phantoms with and without Sephadex beads were made to simulate these patterns, and relaxation parameters were measured using a 1.5-T clinical scanner. Finally, these results were compared to clinical image data using SPIO particulate agent. Intravital microscopy indicated that the clustering of latex beads was more predominant in hepatic Kupffer cells than in splenic macrophages (P < 0

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Superparamagnetic iron oxide particles, a new class of contrast agents for MRI, are extremely good enhancers of proton relaxation. However, the development of such particle systems has resulted in a wide range of preparations whose physico-chemical properties differ greatly. We have conducted a set of physical experiments: X ray diffraction analysis, relaxivity measurements, susceptibility determinations, and thermomagnetic cycling on different preparations of superparamagnetic particles. Our results demonstrate a good correlation between susceptibilities measured in liquid samples at room temperature and the R2/R1 ratio. Susceptibility measurements between liquid nitrogen temperature and room temperature show three different types of behavior dependent on the size of iron oxide crystals. Comparison of heating and cooling curves from strong field thermomagnetic cycles provides information about the maghemite/magnetite crystal content. The information on magnetic properties reported in this study may help to characterize and to select these materials for use as MRI contrast agents.