PURPOSE: To investigate the accumulation and cellular uptake of long-circulating dextran-coated iron oxide (LCDIO) particles in malignant neoplasms in vivo. MATERIALS AND METHODS: A gliosarcoma rodent model was established to determine the distribution of a model LCDIO preparation in tumors. LCDIO accumulation in tissue sections was evaluated with multichannel fluorescence microscopy with rhodaminated LCDIO, green fluorescent protein as a tumor marker, and Hoechst 33258 dye as an intravital endothelial stain. Uptake into tumor cells was corroborated with results of immunohistochemical and cell culture uptake experiments. The effect of intratumoral LCDIO uptake on magnetic resonance (MR) imaging signal intensity was evaluated with a 1.5-T superconducting magnet. RESULTS: Tumoral accumulation of LCDIO was 0.11% ± 0.06 of the injected dose per gram of tissue in brain tumors and was sufficient for detection at MR imaging. In tumor sections, LCDIO was preferentially localized in tumor cells (49.0% ± 4.6) but w...