Pharmacokinetics of a triarylmethyl-type paramagnetic spin probe used in EPR oximetry

Abstract

The paramagnetic spin probe Oxo63 is used in oximetric imaging studies based on electron paramagnetic resonance (EPR) methods by monitoring the oxygen-dependent linewidth while minimizing the contributions from self-broadening seen at high probe concentrations. Therefore, it is necessary to determine a suitable dose of Oxo63 for EPR-based oxygen mapping where the self-broadening effects are minimized while signal intensity adequate for imaging can be realized. A constant tissue concentration of spin probe would be useful to image a subject and assess changes in pO₂ over time; accumulation or elimination of the compound in specific anatomical regions could translate to and be mistaken for changes in local pO₂, especially in OMRI-based oximetry. The in vivo pharmacokinetics of the spin probe, Oxo63, after bolus and/or continuous intravenous infusion was investigated in mice using a novel approach with X-band EPR spectroscopy. The results show that the half-life in blood was 17-21 min and the clearance by excretion was 0.033-0.040 min⁻¹. Continuous infusion following a bolus injection of the probe was found to be effective to obtain stable plasma concentration as well as image intensity to permit reliable pO₂ estimates.