title: Diamagnetic Imaging Agents with a Modular Chemical Design for Quantitative Detection of β-Galactosidase and β-Glucuronidase Activities with CatalyCEST MRI.
abstract: Imaging agents for the noninvasive in vivo detection of enzyme activity in preclinical and clinical settings could have fundamental implications in the field of drug discovery. Furthermore, a new class of targeted prodrug treatments takes advantage of high enzyme activity to tailor therapy and improve treatment outcomes. Herein, we report the design and synthesis of new magnetic resonance imaging (MRI) agents that quantitatively detect β-galactosidase and β-glucuronidase activities by measuring changes in chemical exchange saturation transfer (CEST). Based on a modular approach, we incorporated the enzymes' respective substrates to a salicylate moiety with a chromogenic spacer via a carbamate linkage. This furnished highly selective diamagnetic CEST agents that detected and quantified enzyme activities of glycoside hydrolase enzymes. Michaelis-Menten enzyme kinetics studies were performed by monitoring catalyCEST MRI signals, which were validated with UV-vis assays.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Fernández-Cuervo
authors.affiliation: Department of Chemistry and Biochemistry, The University of Arizona , 1306 East University Blvd, Tucson, Arizona 85719, United States.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Tucker
authors.forename: Scott W
authors.initials: SW
authors.lastname: Malm
authors.affiliation: Department of Biomedical Engineering, The University of Arizona , 1127 East James E. Rogers Way, P.O. Box 210020, Tucson, Arizona 85721, United States.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Jones
authors.affiliation: Department of Chemistry and Biochemistry, The University of Arizona , 1306 East University Blvd, Tucson, Arizona 85719, United States.|Department of Biomedical Engineering, The University of Arizona , 1127 East James E. Rogers Way, P.O. Box 210020, Tucson, Arizona 85721, United States.|Department of Medical Imaging, The University of Arizona , 1515 North Campbell Avenue, Tucson Arizona 85724, United States.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pagel