Detection of Enzyme Activity in a Pancreatic Tumor Model Using CatalyCEST Contrast MRI

Abstract

Detection of enzyme activity has gained popularity in molecular imaging because increased activity of enzymes such as urokinase plasminogen activator (uPA) can serve as biomarkers and assist in cancer diagnosis. Chemical exchange saturation transfer (CEST) Magnetic Resonance Imaging (MRI) is a non-invasive technique that can be utilized to detect enzyme activity; however, CEST MRI is not the only technique that can assess enzyme activity. Chapter 1 provides an overview of various imaging modalities that have been used to detect enzyme activity in vivo. Advances made in probe-design are discussed, in addition to advantages and disadvantages of each technique. Chapter 2 focuses on detection of uPA activity in a pancreatic cancer tumor model using a catalyCEST MRI contrast agent. Chapter 2 also discusses the importance of uPA in tumor biology, addresses the synthesis of the contrast agent, and evaluates the results of in vivo detection and ex vivo validation of uPA activity in response to therapy of pancreatic tumor models of Capan-2. The in vivo and ex vivo results showed no significant difference in uPA activity between chemotherapy-treated and non-treated mice. Additionally, no significant difference was observed between before and after chemotherapy-treated groups. Chapter 3 addresses some of the limitations of the study detailed in Chapter 2 and proposes improvements.