Fluorinated Metal Complexes as MRI Contrast Agents

Abstract

Magnetic resonance imaging (MRI) is a vital tool in today’s modern healthcare system. MRI is preferred over positron emission tomography (PET) and X-ray computed tomography (CT) because it is non-invasive, non-radioactive, and provides 3-D imaging directly in vivo. Contrast agents are used in order to enhance the resolution of the images from MRI. All currently used contrast agents are based on gadolinium and image water protons in the human body. However, gadolinium-based contrast agents are principally unable to quantitatively image specific biomarkers of diseased states, lacking a ratiometric mechanism. Fluorine-based MRI does not suffer from these limitations, but its low sensitivity, with a limit of detection (LOD) in the micromolar range first requires a contrast agent designed specifically to address this issue of sensitivity, which can be accomplished using contrast agents with an incorporated lanthanide center. Fluorine MRI eliminates background signals and has a large chemical shift range which enables fluorines in different environments to each be imaged independently. This in turn allows for the development of ratiometric, responsive contrast agents whereby the total probe concentration and the concentration of the analyte can be independently determined. In this thesis, the theory, practicality, utility, and potential for fluorine-based MRI contrast agents is described. Sensitivity is addressed, synthesis is described, and demonstrations of the potential for fluorine MRI are examined in vitro and in vivo in order to design highly-sensitive, responsive, and biocompatible fluorine contrast agents.