|Title||A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Hingorani DV, Montano LA, Randtke EA, Lee YSun, Cárdenas-Rodríguez J, Pagel MD|
|Journal||Contrast Media Mol Imaging|
|Date Published||2016 Mar-Apr|
|Keywords||Amides, Amines, Catalysis, Cathepsin B, Contrast Media, Ligands, Magnetic Resonance Imaging, Molecular Imaging, Water|
CatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non-responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme-responsive and enzyme-unresponsive CEST signals was synthesized and characterized. The CEST signal from the aryl amide disappeared after cleavage of a dipeptidyl ligand with cathepsin B, while a salicylic acid moiety was largely unresponsive to enzyme activity. The ratiometric comparison of the two CEST signals from the same agent allowed for concentration independent measurements of enzyme activity. The chemical exchange rate of the salicylic acid moiety was unchanged after enzyme catalysis, which further validated that this moiety was enzyme-unresponsive. The temperature dependence of the chemical exchange rate of the salicylic acid moiety was non-Arrhenius, suggesting a two-step chemical exchange mechanism for salicylic acid. The good detection sensitivity at low saturation power facilitates clinical translation, along with the potentially low toxicity of a non-metallic MRI contrast agent. The modular design of the agent constitutes a platform technology that expands the variety of agents that may be employed by catalyCEST MRI for molecular imaging.
|Alternate Journal||Contrast Media Mol Imaging|
|PubMed Central ID||PMC4882611|
|Grant List||R01CA167183-01 / CA / NCI NIH HHS / United States |
R01 CA169774 / CA / NCI NIH HHS / United States
P50 CA095060 / CA / NCI NIH HHS / United States
R01 CA167183 / CA / NCI NIH HHS / United States
P50 CA95060 / CA / NCI NIH HHS / United States
A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals.
Faculty Member Reference:
Yeon Sun Lee, Ph.D.