A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals. (3rd December 2015)

• Record Type: Journal Article
• Authors: Hingorani, Dina V.; Montano, Luis A.; Randtke, Edward A.; Lee, Yeon Sun; Cárdenas‐Rodríguez, Julio; Pagel, Mark D.
• Is Part Of: Contrast media & molecular imaging. Volume 11:Number 2(2016:Mar./Apr.)
• Page Start: 130
• Page End: 138
• Publication Date: 2015-12-03
• Subjects: CEST MRI -- enzyme activity -- cathepsin B -- ratiometric analysis; Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1672
• Languages: English
• ISSNs: 1555-4309

Abstract

Abstract : 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. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : A catalyCEST MRI contrast agent with enzyme‐responsive and enzyme‐ unresponsive CEST signals was developed to detect cathepsin B activity. The ratio of CEST signals was used to improve the detection of cathepsin B activity. The modular design of the agent is a platform technology that can improve catalyCEST MRI for molecular imaging.