A responsive MRI contrast agent to monitor functional cell status.
It has been shown that insoluble Gd chelates are suitable MRI contrast agents for conditional activation by intracellular lipases. The DTPA-based, insoluble, inactive contrast agent was internalized into dendritic cells by phagocytosis. Cleavage of long aliphatic side chains by intracellular lipase activity leads to the contrast agents solubility and hereby its activation depending on the enzyme expression. Uptake and activation of the contrast agent was much reduced in Flt3+ CD11b+ progenitor cells. Detectability limits in the T(1)-weighted MR images were estimated in phantoms and in vivo in the rat brain. Marginal toxic effects were only observed at very high concentrations of the contrast agent. The chelate can easily be modified to be targeted by enzymes expressed during specific change of cell status like activation or differentiation. Such a system is suitable for functional cellular in vivo MR imaging.
Himmelreich
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In-vivo-NMR-laboratory, Max-Planck-Institute for Neurological Research, Klaus-Joachim-Zülch-Laboratories/Max-Planck-Society, and Faculty of Medicine, University of Cologne, Gleueler Strasse 50, Cologne D-50931, Germany. himmelreich@nf.mpg.de
Aime
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Hieronymus
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Justicia
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Uggeri
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Zenke
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Hoehn
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D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D001921:Brain / Q000166:cytology*; D002468:Cell Physiological Phenomena; D017690:Cell Transplantation / Q000502:physiology*; D003287:Contrast Media / Q000633:toxicity; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology; D019786:Gadolinium DTPA / Q000633:toxicity; D020869:Gene Expression Profiling; D008049:Lipase / Q000096:biosynthesis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008953:Models, Anatomic; D020411:Oligonucleotide Array Sequence Analysis; D018075:RNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000502:physiology
D003287:Contrast Media; D018076:DNA, Complementary; D018075:RNA, Complementary; D008049:Lipase; D019786:Gadolinium DTPA