Dual Hydrazine-Equipped Turn-On Manganese-Based Probes for Magnetic Resonance Imaging of Liver Fibrogenesis.
Yingying NingIris Yuwen ZhouNicholas J RotilePamela PantazopoulosHuan WangStephen Cole BarrettMozhdeh SojoodiKenneth K TanabePeter CaravanPublished in: Journal of the American Chemical Society (2022)
Liver fibrogenesis is accompanied by upregulation of lysyl oxidase enzymes, which catalyze oxidation of lysine ε-amino groups on the extracellular matrix proteins to form the aldehyde containing amino acid allysine (Lys Ald ). Here, we describe the design and synthesis of novel manganese-based MRI probes with high signal amplification for imaging liver fibrogenesis. Rational design of a series of stable hydrazine-equipped manganese MRI probes gives Mn-2CHyd with the highest affinity and turn-on relaxivity (4-fold) upon reaction with Lys Ald . A dynamic PET-MRI study using [ 52 Mn]Mn-2CHyd showed low liver uptake of the probe in healthy mice. The ability of the probe to detect liver fibrogenesis was then demonstrated in vivo in CCl 4 -injured mice. This study enables further development and application of manganese-based hydrazine-equipped probes for imaging liver fibrogenesis.
Keyphrases
- living cells
- fluorescent probe
- magnetic resonance imaging
- small molecule
- extracellular matrix
- contrast enhanced
- fluorescence imaging
- computed tomography
- amino acid
- high resolution
- single molecule
- magnetic resonance
- nucleic acid
- diffusion weighted imaging
- room temperature
- cell proliferation
- sensitive detection
- signaling pathway
- metabolic syndrome
- high fat diet induced
- quantum dots
- nitric oxide
- mass spectrometry
- ionic liquid
- liver fibrosis
- wild type