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Experimental Studies |
1 From the Department of Radiology, Center for Molecular Imaging Research, Massachusetts General Hospital, Bldg 149, 13th St, 5403, Charlestown, MA 02129. Received February 1, 1999; revision requested March 15; revision received March 26; accepted June 28. Supported in part by National Institutes of Health grant nos. 5-RO1-NS335258-03, 5-RO1-CA54886-06, RO1-CA7442401 and 2-RO1-CA5964905. E.M. supported by a Fellowship Award from the Center for Innovative Minimally Invasive Therapy (CIMIT) at Massachusetts General Hospital. Address reprint requests to R.W. (e-mail: weissleder@helix.mgh.harvard.edu).
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 was also taken up by macrophages in tumors (21.0% ± 3.1) and by endothelial cells in the areas of active angiogenesis (6.5% ± 1.4). In cell culture, LCDIO uptake was strongly correlated with growth rate of tumor cell lines.
CONCLUSION: Tumoral LCDIO accumulation was not negligible and helped explain MR imaging signal intensity changes observed in clinical trials. Microscopically, LCDIO accumulated predominantly in tumor cells and tumor-associated macrophages. Uptake into tumor cells appeared to be directly proportional to cellular proliferation rates.
Index terms: Animals • Brain, iron • Brain neoplasms, 10.363 • Brain neoplasms, MR, 10.121412, 10.12146 • Contrast media, experimental studies • Iron • Neoplasms, experimental studies, 10.363
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