Self-Immolative Activation of β-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models

Laura M. Lilley, Sarah Kamper, Michael Caldwell, Zer Keen Chia, David Ballweg, Luke Vistain, Jeffrey Krimmel, Teresa Anne Mills, Keith MacRenaris, Paul Lee, Emily Alexandria Waters, Thomas J. Meade*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-gal activity by modulating the coordination of water to GdIII. The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the GdIII ion. This renders the agent ineffective. We show that one agent in particular (6-C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β-gal.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalAngewandte Chemie - International Edition
Volume59
Issue number1
DOIs
StatePublished - Jan 2 2020

Keywords

  • imaging agents
  • macrocyclic ligands
  • magnetic resonance
  • self immolative activation
  • β-galactosidase

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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