Abstract

The cellular effects of a reticuloendothelial contrast agent for MR imaging were examined in cultured murine macrophages (J774 cells). The macrophage handling and toxicity of iron oxide loaded starch microspheres (MSM) were evaluated by radiotracer studies, relaxation time analysis, electron microscopy and a cytotoxicity assay (MTT test). Macrophages exposed to MSM showed a concentration-dependent and saturable accumulation of the microspheres. MSM were intracellularly localized to the lysosomes. Relaxation time measurements indicated that the iron oxide in MSM was mobilized and eliminated from the cells. The cellular toxicity of MSM was investigated after various incubation times and no cytotoxicity of MSM or components of MSM was detected, whereas ionic iron administred directly to J744 cells showed high cellular toxicity. This study has shown that starch microspheres containing iron oxide are nontoxic to macrophages in vitro. Consequently, MSM is an attractive delivery system for targeting of MR contrast agents to the reticuloendothelial system.

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