Abstract
The glutamine transporting system is up-regulated in tumor cells because cell proliferation requires the uptake of large quantities of glutamine. It has been found that the paramagnetic magnetic resonance imaging (MRI) reporter Gd-DOTAMA-C6-Gln, where the glutamine residue is covalently bound to the Gd chelate through a C6 spacer, accumulates in tumor cells both "in vitro" and "in vivo" experiments. The observation that the relaxivity of cellular pellets does not increase with the increase in the amounts of entrapped Gd chelate is taken as an indication that the internalization has occurred through receptor mediated endocytosis. The iv administration of Gd-DOTAMA-C6-Gln allowed the MRI visualization of tumor masses in A/J mice grafted with the murine neuroblastoma cell line Neuro-2a and in Her-2/neu transgenic mice developing multiple mammary carcinoma, respectively.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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Chelating Agents / chemical synthesis
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Contrast Media* / pharmacokinetics
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Female
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Gadolinium*
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Glutamine / metabolism*
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Heterocyclic Compounds, 1-Ring / chemistry
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Humans
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Magnetic Resonance Imaging
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Mammary Neoplasms, Experimental / diagnosis
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Mammary Neoplasms, Experimental / pathology
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Mice
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Mice, Transgenic
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Neoplasms, Experimental / diagnosis*
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Neoplasms, Experimental / pathology
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Organometallic Compounds / chemical synthesis*
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Organometallic Compounds / pharmacokinetics
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Rats
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Receptor, ErbB-2 / genetics
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Transplantation, Heterologous
Substances
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Carrier Proteins
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Chelating Agents
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Contrast Media
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Heterocyclic Compounds, 1-Ring
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Organometallic Compounds
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glutamine transport proteins
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Glutamine
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1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
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Gadolinium
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Receptor, ErbB-2