In vivo spin-label murine pharmacodynamics using low-frequency electron paramagnetic resonance imaging.
A novel, very-low-frequency electron paramagnetic resonance (EPR) technique is used to image the distribution of several nitroxides with distinct pharmacologic compartment affinities in the abdomens of living mice. 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 imaging to distinguish a single spatial dimension. Liver and bladder of the mouse anatomy are distinguished by this technique. After an intraperitoneal 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 shift 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 will provide a new method of magnetic resonance imaging for determination of pharmacodynamics in the body of an intact animal.
Halpern
H J
HJ
Department of Radiation and Cellular Oncology, University of Chicago, Illinois 60637, USA. h-halpern@uchicago.edu
Peric
M
M
Yu
C
C
Barth
E D
ED
Chandramouli
G V
GV
Makinen
M W
MW
Rosen
G M
GM
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D019047:Phantoms, Imaging; D011759:Pyrrolidines / Q000737:chemistry / Q000493:pharmacokinetics; D013113:Spin Labels; D014018:Tissue Distribution
D003497:Cyclic N-Oxides; D011759:Pyrrolidines; D013113:Spin Labels; C037782:2,2,5,5-tetramethyl-1-oxy-3-pyrroline-3-carboxylic acid; C047253:3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-1-yloxyl