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A Highly Sensitive Biocompatible Spin Probe for Imaging of Oxygen Concentration in Tissues

Center for Biomedical EPR Spectroscopy and Imaging, Comprehensive Cancer Center, Davis Heart and Lung Research Institute, Department of Internal Medicine, The Ohio State University, Columbus, Ohio

Correspondence: Address reprint requests to Periannan Kuppusamy, Tel.: 614-292-8998; E-mail: kuppusamy.1{at}osu.edu.

The development of an injectable probe formulation, consisting of perchlorotriphenylmethyl triester radical dissolved in hexafluorobenzene, for in vivo oximetry and imaging of oxygen concentration in tissues using electron paramagnetic resonance (EPR) imaging is reported. The probe was evaluated for its oxygen sensitivity, biostability, and distribution in a radiation-induced fibrosarcoma tumor transplanted into C3H mice. Some of the favorable features of the probe are: a single narrow EPR peak (anoxic linewidth, 41 µT), high solubility in hexafluorobenzene (>12 mM), large linewidth sensitivity to molecular oxygen (1.8 µT/mmHg), good stability in tumor tissue (half-life: 3.3 h), absence of spin-spin broadening (up to 12 mM), and lack of power saturation effects (up to 200 mW). Three-dimensional spatial and spectral-spatial (spectroscopic) EPR imaging measurements were used to visualize the distribution of the probe, as well as to obtain spatially resolved pO₂ information in the mice tumor subjected to normoxic and hyperoxic treatments. The new probe should enable unique opportunities for measurement of the oxygen concentration in tumors using EPR methods.

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