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Tumor Cell Endocytosis Imaging Facilitates Delineation of the Glioma–Brain Interface

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Abstract

We describe a method for measuring tumor cell endocytosisin vivoand provide the anatomic correlate of this tumor cell function using a superparamagnetic and histologically detectable marker for cell uptake (MION). Rats (n = 22) were intrahemispherically implanted with a thymidine kinase (TK)-positive 9L gliosarcoma cell line, where TK served as the tumor marker. Twenty-four hours after intravenous injection of 10 mg Fe/kg of MION, rat brains were removed and underwent MR imagingex vivoat near-microscopic resolution (isotropic voxel size of 86 μm, 9.4 T) prior to histologic processing. The imaging probe accumulated within tumor cells adjacent to the hyperpermeable tumor–brain interface including microscopic deposits and along finger-like invasions of the tumor into brain, facilitating the demarcation of the true histologic tumor border in three dimensions by MR microscopy. The method has potential research and clinical implications for delineating the tumor–brain interface prior to therapy and/or for providing a rational basis for imaging nanocolloid drug delivery to solid tumors.

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Supported in part by NIH 2RO1 CA54886-04A1 and 5RO1CA59649-03, and in part by NIH Grant P41 RR05959. C.Z. was supported by the Deutsche Forschungsgemeinschaft (Zi 477/1-1).

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