Proton electron double resonance imaging of the in vivo distribution and clearance of a triaryl methyl radical in mice

Proton electron double resonance imaging (PEDRI) measures the spatial distribution of paramagnetic species in biological samples using the Overhauser effect. Triaryl methyl (TAM) free radicals have been developed as a spin probe for PEDRI since they have very long T_1e. Therefore, low RF power levels are sufficient to saturate the electron spin system with resultant high NMR enhancement facilitating application of PEDRI in living animals. In this report, PEDRI studies were performed at 0.02 T. The power-dependent image enhancement was studied using phantoms of TAM in saline, then the distribution and pharmacokinetics of TAM in living mice were measured. Following intravenous administration of 0.7 mmol/kg of TAM, enhancements of up to -34 were observed enabling visualization of its distribution within the body. Maximum uptake of TAM in the vascular compartment was seen 1 min postadministration with half-clearance within 5 min. Maximum uptake in the kidneys occurred at 10 min with half-clearance at 26 min and maximum accumulation in the bladder after 50 min. Thus, TAM is initially compartmentalized in the vasculature and this is followed by rapid uptake and excretion by the kidneys. PEDRI enabled rapid imaging of the distribution and clearance of this paramagnetic probe and this information should facilitate the use of TAM as a label for oximetry and other applications.