Imaging the tissue distribution of glucose in livers using a PARACEST sensor

Noninvasive imaging of glucose in tissues could provide important insights about glucose gradients in tissue, the origins of gluconeogenesis, or perhaps differences in tissue glucose utilization in vivo. Direct spectral detection of glucose in vivo by (1)H NMR is complicated by interfering signals from other metabolites and the much larger water signal. One potential way to overcome these problems is to use an exogenous glucose sensor that reports glucose concentrations indirectly through the water signal by chemical exchange saturation transfer (CEST). Such a method is demonstrated here in mouse liver perfused with a Eu(3+)-based glucose sensor containing two phenylboronate moieties as the recognition site. Activation of the sensor by applying a frequency-selective presaturation pulse at 42 ppm resulted in a 17% decrease in water signal in livers perfused with 10 mM sensor and 10 mM glucose compared with livers with the same amount of sensor but without glucose. It was shown that livers perfused with 5 mM sensor but no glucose can detect glucose exported from hepatocytes after hormonal stimulation of glycogenolysis. CEST images of livers perfused in the magnet responded to changes in glucose concentrations demonstrating that the method has potential for imaging the tissue distribution of glucose in vivo.