Yuguo Li1, Vipul R Sheth2, Guanshu Liu3,4, 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 T1sat relaxation time, providing a more accurate way to detect esterase enzyme activity without needing a reference agent.