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An enzyme-activatable and cell-permeable MnIII-porphyrin as a highly efficient T1 MRI contrast agent for cell labeling1

Haedicke, Inga E. et al.

Chemical science. Volume 7:Issue 7 (2016); pp 4308-4317 -- Royal Society of Chemistry

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  • Title:
    An enzyme-activatable and cell-permeable MnIII-porphyrin as a highly efficient T1 MRI contrast agent for cell labeling1
  • Author: Haedicke, Inga E.;
    Li, Tan;
    Zhu, Yong Le K.;
    Martinez, Francisco;
    Hamilton, Amanda M.;
    Murrell, Donna H.;
    Nofiele, Joris T.;
    Cheng, Hai-Ling M.;
    Scholl, Timothy J.;
    Foster, Paula J.;
    Zhang, Xiao-an
  • Found In: Chemical science. Volume 7:Issue 7 (2016); pp 4308-4317
  • Journal Title: Chemical science
  • Subjects: Chemistry--Periodicals; Dewey: 540.5
  • Rights: legaldeposit
  • Publication Details: Royal Society of Chemistry
  • Abstract: Abstract :

    MnAMP, a cell-trappable pro-contrast agent gets enzymatically activated and accumulated intracellularly to provide a strong MRI signal for cell labeling.

    Abstract :

    Magnetic resonance imaging (MRI) is a preferred technique for noninvasively monitoring the fate of implanted cells, such as stem cells and immune cells in vivo . Cellular MRI requires contrast agents (CAs) to label the cells of interest. Despite promising progress made in this emerging field, highly sensitive, stable and biocompatible T 1CAs with high cell permeability and specificity remains an unmet challenge. To address this need, a novel Mn III -porphyrin, MnAMP was designed and synthesized based on the modification of Mn III tetra(carboxy-porphyrin) (MnTCP), a small and highly stable non-Gd extracellular CA with good biocompatibility and high T 1relaxivity ( r 1= 7.9 mM −1 s −1 ) at clinical field of 3 Tesla (T). Cell permeability was achieved by masking the polar carboxylates of MnTCP with acetoxymethyl-ester (AM) groups, which are susceptible to hydrolysis by intracellular esterases. The enzymatic cleavage of AM groups led to disaggregation of the hydrophobic MnAMP, releasing activated MnTCP with significant increase in T 1relaxivity. Cell uptake of MnAMP is highly efficient as tested on two non-phagocytic human cell lines with no side effects observed on cell viability. MRI of labeled cells exhibited significant contrast enhancement with a short T 1of 161 ms at 3 T, even though a relatively low concentration of MnAMP and short incubation time was applied for cell labeling. Overall, MnAMP is among the most efficient T 1cell labeling agents developed for cellular MRI.

  • Identifier: System Number: LDEAvdc_100047596274.0x000001; Journal ISSN: 2041-6520; 10.1039/c5sc04252f
  • Publication Date: 2016
  • Physical Description: Electronic
  • Shelfmark(s): ELD Digital store

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