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

Content Provider	Royal Society of Chemistry (RSC)
Author	Hamilton, Amanda M. Li, Tan Zhang, Xiao-an Martinez, Francisco Haedicke, Inga E. Foster, Paula J. Zhu, Yong Le K. Murrell, Donna H. Cheng, Hai-Ling M. Scholl, Timothy J. Nofiele, Joris T.
Copyright Year	2016
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 T1 CAs with high cell permeability and specificity remains an unmet challenge. To address this need, a novel MnIII-porphyrin, MnAMP was designed and synthesized based on the modification of MnIIItetra(carboxy-porphyrin) (MnTCP), a small and highly stable non-Gd extracellular CA with good biocompatibility and high T1 relaxivity (r1 = 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 T1 relaxivity. 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 T1 of 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 T1 cell labeling agents developed for cellular MRI.
Starting Page	4308
Ending Page	4317
Page Count	10
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	7
Issue Number	7
Journal	Chemical Science
DOI	10.1039/c5sc04252f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Subscribed
Subject Keyword	Hydrolysis Semipermeable membrane Magnetic resonance imaging Biocompatibility Amplitude modulation Nikola Tesla Hydrophobe
Content Type	Text
Resource Type	Article
Subject	Chemistry

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