A CEST MRI method to measure pH

Tumor pH is an important biomarker in cancer. In the following chapters an approach to measure pH by Chemical Exchange Saturation Transfer (CEST) MRI is described. Chapter 1 presents and introduction to molecular imaging, the importance of tumor pH and existing methods of pH measurement by various imaging modalities. Chapter 2 describes the characterization of a PARACEST MRI contrast agent, Yb-DO3A-oAA, for pH measurement. The pH measurement is independent of concentration and T1sat relaxation times, and covers a wider pH measurement range than alternative methods. A new method for fitting PARACEST spectra is shown. Chapter 3 demonstrates the self calibrating nature of CEST MRI with the contrast agent, Yb-DO3A-oAA-TML-ester, to detect esterase enzyme activity in solution and in cell culture media by generating an enzyme-responsive CEST effect that was compared with a control CEST effect from the same agent. In Chapter 4, a new MRI method was developed to simplify MRI acquisition of CEST spectra. Arrayed CEST-FISP and the parameters of this method were optimized for use with PARACEST agents. The arrayed CEST-FISP pulse program simplifies acquisition setup and subsequent analysis, and has strong potential to increase CEST experimental throughput that will facilitate future discoveries. Chapter 5 translates Yb-DO3A-oAA from in vitro to in vivo use to measure pH in a MDA-MB-231 tumor model and mouse muscle. The pharmacodynamics of Yb-DO3A-oAA are investigated and the fitting algorithm described in Chapter 2 is extended to in vivo tissues.