A responsive MRI contrast agent to monitor functional cell status
Himmelreich, Uwe × Aime, S Hieronymus, T Justicia, C Uggeri, F Zenke, M Hoehn, M #
NeuroImage vol:32 issue:3 pages:1142-1149
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. (c) 2006 Elsevier Inc. All rights reserved.