In vivo spin-label murine pharmacodynamics using low-frequency electron paramagnetic resonance imaging

Abstract

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.

Clearance and Biodistribution of Liposomally Encapsulated Nitroxides: A Model for Targeted Delivery of Electron Paramagnetic Resonance Imaging Probes to Tumors

“…Although the nitroxides used in this study were specifically designed to resist bioreduction (Keana et al, 1987;Halpern et al, 1996), bioreduction can still occur. This could account for relatively less nitroxide being found in the liver compared with 67 Ga, the clearance of which from the liver occurs over days to months (Dudley et al, 1949).…”

Cyclic nitroxide radicals attenuate inflammation and Hyper-responsiveness in a mouse model of allergic asthma

“…Nitroxides given by almost any route distribute virtually instantaneously throughout all tissues, and therefore, do not require early administration [48,[55][56][57]. However, nitroxides do not accumulate but are rather progressively depleted via reduction to their respective hydroxylamines and clearance from the circulation [48][49][50][51][52]54].…”

A new strategy for fast radiofrequency CW EPR imaging: Direct detection with rapid scan and rotating gradients

“…Since free radicals in situ are at very low concentration and most of them are short-lived, in vivo EPR imaging requires the introduction, via intravenous or intramuscular injection or implantation, of stable non-toxic free radical spin probes into the animal. Stable nitroxides and triarylmethyl radicals (TAMs) are being routinely used as probes to obtain physiologic information [4,5]. Both pulsed and CW methods have been developed for the purpose of small animal functional EPR imaging [6][7][8].…”