IN-VIVO SPIN-LABEL MURINE PHARMACODYNAMICS USING LOW-FREQUENCY ELECTRON-PARAMAGNETIC-RESONANCE IMAGING

A novel, very-low-frequency electron paramagnetic resonance (EPR) tech nique is used to image the distribution of several nitroxides with dis tinct pharmacologic compartment affinities in the abdomens of living m ice. Image acquisition is sufficiently rapid to allow a time sequence of the distribution for each compound. The spectra and concentrations of these nitroxides are imaged with the use of spectral-spatial imagin g to distinguish a single spatial dimension. Liver and bladder of the mouse anatomy are distinguished by this technique. After an intraperit oneal injection of the spin-label probes, a shift in the distribution of the compounds from the upper abdomen (primarily liver) to the lower abdomen (primarily bladder) is observed. The time dependence of the s hift in regional distribution depends on the structural properties of the side chain attached to the spin label. These results indicate that this application of in vivo electron paramagnetic resonance imaging w ill provide a new method of magnetic resonance imaging for determinati on of pharmacodynamics in the body of an intact animal.