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Abstract #1036

Detecting in vivo urokinase Plasminogen Activator activity with a catalyCEST MRI contrast agent

Sanhita Sinharay1, Christine M. Howison2, Amanda F. Baker3, and Mark D. Pagel2

1Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 2Medical Imaging, University of Arizona, Tucson, AZ, United States, 3University of Arizona Cancer Center, University of Arizona, Tucson, AZ, United States

SYNOPSIS: We have designed a nonmetallic contrast agent, GR-4Am-SA, that can detect the activity of urokinase Plasminogen Activator with CEST MRI. uPA cleaves a peptide of the agent which causes CEST at 5.0 ppm to decrease, but CEST at 9.5 ppm is unchanged. The two CEST signals were used to determine a reaction coordinate, representing the extent of enzyme-catalyzed cleavage of the GR-4Am-SA agent. GR-4Am-SA detected uPA activity in solution, and in a flank xenograft model of Capan-2 pancreatic cancer.

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