Dynamic Electron Paramagnetic Resonance Imaging: Modern Technique for Biodistribution and Pharmacokinetic Imaging

Abstract

The imaging of the biodistribution and pharmacokinetics is critical in understanding the complexity of drug delivery mechanisms, the status of the disease, and the monitoring of the treatment progress. The imaging techniques, such as magnetic resonance imaging, computed tomography, and positron emission tomography, are suitable for clinical applications. However, with regards to the biodistribution and pharmacokinetics, their availability is often limited due to the requirements of ionizing radiation or high magnetic fields, low spatial and temporal resolution (applicable for animals), and high maintenance costs. Electron paramagnetic resonance (EPR) imaging is a technique that allows for the minimal invasive mapping of unique parameters, such as the oxygen concentration, the redox state, the thiol concentration, or the pH level, in vivo. In this work, a high temporal resolution 3D EPR imaging technique was used for assessing the trityl spin probe pharmacokinetics in mice. The results demonstrate the preliminary outcomes in the application of EPR imaging for the comparison of the trityl spin probe pharmacokinetics between that of a healthy mouse and a tumor-bearing mouse. This study will stimulate further investigation into the use of imaging strategies, such as EPR imaging, to analyze pharmacokinetics.

Redox-Sensitive Mapping of a Mouse Tumor Model Using Sparse Projection Sampling of Electron Paramagnetic Resonance

“…Therefore, 1 H-MRI-based redox mapping required a higher dose of nitroxyl radicals (Tempol, 1.6 mol/g body weight) (19). This dose is 1.8-fold higher than our 15 N-PDT dose (0.9 mol/g body weight) (see Materials and Methods).…”

“…In previous studies, redox mapping of mouse tumor-bearing legs was performed with 1 H-MRI using signal enhancement due to exogenously injected nitroxyl radicals (19,34). In the literature (19), Tempol has also been used for redox mapping of tumors.…”

“…An advantage of EPR-based redox-sensitive mapping is the higher sensitivity to nitroxyl radicals. 1 H-MRI-based redox mapping uses signal enhancement due to nitroxyl radicals. Therefore, 1 H-MRI indirectly detects the redox state through the contrast enhancement of nitroxyl radicals.…”

“…1 H-MRI-based redox mapping uses signal enhancement due to nitroxyl radicals. Therefore, 1 H-MRI indirectly detects the redox state through the contrast enhancement of nitroxyl radicals. Nevertheless, the contrast enhancement in MRI with nitroxyl radicals is weaker than that of clinically used gadolinium contrast agents.…”

“…Moreover, 1 H-MRI provides an anatomical map of a subject animal and image-contrast for tumor tissues. These features are advantageous in co-imaging EPR-based decay rates and MR anatomical information (Figs.…”