New frontiers and developing applications in 19F NMR

1.1 Overview 19F NMR is gaining interest as a tool for diverse physiological and pharmaceutical investigations as evidenced by new reporter molecules and detection strategies. The relatively high sensitivity of 19F and lack of interfering background signal in the body have enabled the observation of exogenously administered agents and their metabolites. The 19F nucleus exhibits a large chemical shift range (~300 ppm), which is exquisitely sensitive to the electronic microenvironment, and many reporter molecules have been developed. In addition to chemical shift studies, relaxation processes (R1 and R2), and chemical exchange have also been tailored to be responsive to a parameter of interest such as pO2, pH, metal ion concentrations, transgene/enzyme activity or hypoxia. Recent emphasis has been on enhancing signal sensitivity and developing novel response mechanisms to sense environmental parameters. This review focuses on quantitative tissue oximetry, detection of ions including pH, and detection of enzyme activity. Fluorine NMR has been widely exploited for laboratory investigations and is garnering developing use in pre-clinical applications for small animals in vivo.