Abstract
This article aimed at reviewing the advances on the development of paramagnetic complexes used as chemical exchange saturation transfer agents in magnetic resonance imaging. This relatively new type of contrast opens new avenues in the development of MRI probes for molecular imaging, and coordination chemistry lies at the center of such advances. Strategies to detect important biomarkers such as pH, cations, anions, metabolites, enzyme, and O2 were described. The current challenges, limitations, and opportunities in this field of research were discussed.
Highlights
Molecular imaging is gaining increasing interest due to the possibilities to image and understand biochemical processes and to provide early-diagnosis of pathologies
Both chemical exchange saturation transfer (CEST) effects are dependent on the pH, but their ratio shows an excellent correlation with pH [13], which allowed the successful use of this probe for pH determination in vivo [12,22]
Lanthanide complexes represent the majority of responsive ParaCEST probes, transition metal chelates are gaining importance as well
Summary
Molecular imaging is gaining increasing interest due to the possibilities to image and understand biochemical processes and to provide early-diagnosis of pathologies. A similar method has been explored with Yb(DO3A-oAA) (Scheme 1), which shows simultaneously two CEST effects arising from the protons of the amine and the amide groups In this case, both CEST effects are dependent on the pH, but their ratio shows an excellent correlation with pH [13], which allowed the successful use of this probe for pH determination in vivo [12,22]. One of the flaws of ParaCEST MRI is its low sensitivity, which requires using quite important concentrations of contrast agents (typically in the mM range) To circumvent this problem and increase the sensitivity of the probes, Yb(DOTAM) complexes (Scheme 1) have been conjugated to poly(propylene-imine) dendrimers. The large increase of the number of exchangeable amide protons allows for a minimum concentration detected reduced by a factor 4 and 16, respectively, for the first and third generation of dendrimers, with respect to the mononuclear complex [27]
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