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Abstract #3054

Diamagnetic imaging agents with a modular chemical design for quantitative detection of β-galactosidase and β-glucuronidase activities with catalyCEST MRI

Gabriela Fernández-Cuervo1, Kirsten A. Tucker2, Scott W. Malm3, Kyle M. Jones4, and Mark D. Pagel4

1Pharmaceutical Sciences, University of Arizona, Tucson, AZ, United States, 2Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 3Pharmacy, University of Arizona, Tucson, AZ, United States, 4Biomedical Engineering, University of Arizona, Tucson, AZ, United States

We have designed and synthesized new 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 spontaneously disassembling, chromogenic spacer via a carbamate linkage. This design 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.

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