Clinical applications of EPR: overview and perspectives

Abstract

The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO 2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.

Electron Spin Resonance Spectroscopy of Serum Albumin: A Novel New Test for Cancer Diagnosis and Monitoring

“…Results of recent application of ESR spectroscopy in animal models and humans suggest that ESR has great diagnostic potential (10 ). Some promising initial applications include noninvasive, continuous measurement of partial oxygen pressure in tissue and measurement of clinically significant exposure to ionizing radiation (11 ). Another useful application of ESR spectroscopy is in the measurement of structural and functional changes in both soluble and membrane proteins (12 ).…”

Experimental procedures for sensitive and reproducible in situ EPR tooth dosimetry

“…In vivo EPR dosimetry is currently performed using the whole-body clinical EPR spectrometer at the Dartmouth EPR Center (Salikhov, et al, 2005, Swartz, et al, 2006, Swartz, et al, 2004. This continuous wave (CW) spectrometer operates at an L-Band frequency (1.2 GHz) and the main magnetic field is produced by a 420 G permanent magnet with 50 cm pole separation.…”

“…These resonators are equipped with automatic tuning control (ATC) circuitry to minimize effects of subject motion. Detailed descriptions of this clinical spectrometer are given in the published reports (Salikhov, et al, 2005, Swartz, et al, 2004 and specific modifications to the instrument for tooth dosimetry are given here. Descriptions of another dedicated transportable spectrometer for tooth dosimetry have also been published (Swartz, et al, 2006.…”

“…These combined considerations call for the development of a non-invasive means to perform EPR dosimetry. This development is underway at Dartmouth Medical School (Iwasaki, et al, 2005a, Iwasaki, et al, 2005b, Salikhov, et al, 2005, Swartz, et al, 2006, Swartz, et al, 2004 in normal volunteers with irradiated teeth placed in their mouths and initial measurements with patients who have undergone radiation therapy have begun.…”

Implementing EPR dosimetry for life-threatening incidents: Factors beyond technical performance

“…Manufacturers may be willing to invest in the machines for one use -even as a loss leaderbecause of its potential future use in clinical care. For example, clinical uses beyond terrorist related events include: assessing the level of oxygen in tissues to enhance therapy of tumors (because response to radiation therapy for cancer appears to depend on the tumor's current sensitivity to oxygen) and treatment of ischemic diseases, especially peripheral vascular disease in diabetics (because evidence of poor oxygenation of tissues may trigger treatment decisions) (Swartz et al, 2004 While a federal willingness to commit funds to the development of EPR is a positive sign, it falls short of ensuring -even if the device completely fulfills the criteria for performance specified in the contracts-that the Department of Defense will order the devices. Even if the DoD authorizes the purchase of EPR instruments, the implications for manufacturers are rather different if the initial request is for 10 instruments or 1,000--while both numbers currently are quite plausible.…”