Abstract #1675

A Self-Calibrating PARACEST MRI Contrast Agent That Detects Esterase Enzyme Activity

Yuguo Li¹, Vipul R Sheth², Guanshu Liu^3,4, Mark D. Pagel⁵

¹Radiology, Case Western Reserve University, Cleveland, OH, United States; ²Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States; ³Department of Radiology, Johns Hopkins University, Baltimore, MD, United States; ⁴F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States; ⁵Biomedical Engineering & Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

We have developed a new esterase-responsive PARACEST MRI contrast agent. Before esterase cleavage, the agent Yb-DO3A-oAA-TML-ester has only one CEST signal at -11 ppm from an amide proton. Esterase de-esterification forms an amine in the product Yb-DO3A-oAA, which creates a second PARACEST signal at +9 ppm. The two CEST effects of the product endows self-calibration with respect to pharmacokinetic factors such as the concentration of agent and resulting possible shortening of T_1sat relaxation time, providing a more accurate way to detect esterase enzyme activity without needing a reference agent.