Evaluations of pancreatic cancer with acidoCEST MRI

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a virulent disease which readily develops resistances to prevailing chemotherapies. PDAC is often not diagnosed until the disease presents in an inoperable late stage. Early detection of PDAC while there is still hope for effective treatment is critical to survival. Cancer cells experience a metabolic shift towards aerobic glycolysis as they develop. This atypical metabolism results in the production and export of lactic acid, which results in acidification of the extracellular tumor microenvironment. Thus, acidosis is a biomarker of cancer development. Our research program uses a technique called chemical exchange saturation transfer magnetic resonance imaging (acidoCEST MRI) to measure acidosis in the extracellular microenvironment. The work presented in this dissertation will focus on characterization of acidosis in PDAC using acidoCEST MRI. Chapter 1 reviews components of the tumor microenvironment that are affected by acidosis as well as briefly overviews aspects of the microenvironment of pancreatic cancer. Chapter 2 presents work analyzing the role of the glucose transporter GLUT3 in chemoresistance and acidosis of two pancreatic cancer cell lines. Chapter 3 explores the use of acidosis as a prognostic biomarker of pancreatic cancer development. Finally, chapter 4 highlights future studies which would be a natural continuation of the work in this dissertation or would contribute to the advancement of acidoCEST MRI as a research technique.