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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