Pharmacological compartment viscosity and polarity measured with very low‐frequency EPR in tumors of living animals

Abstract

Quantitative measurements of the viscosity of a non-vascular pharmacological compartment in a living animal are presented. Using novel, very low-frequency electron paramagnetic resonance spectroscopy, capable of measurements in humans, novel analytical techniques and partially deuterated spin probes, the viscosity of the body water of murine fibrosarcomas implanted in the leg of a living animal were measured. The average viscosity was 1.9 f 0.2 cP. Variation of the viscosity with tumor size and histology did not appear to be significant.

Biological Applications of Electron Paramagnetic Resonance Viscometry Using a 13C-Labeled Trityl Spin Probe

“…Note that the 13 C-dFT trityl probe is non-permeable to cells and reports on the microviscosity of the extracellular interstitial fluid [28]. On the other hand, the cell-permeable nitroxide probes, e.g., one used by Halpern et al [19,20], report on averaged intracellular and extracellular microviscosity, and therefore may provide complementary information to the measurement using trityl probe.…”

“…Application of low-field EPR increases radiofrequency penetration depth into aqueous samples up to several cm, allowing for in vivo applications. Halpern et al applied 250 MHz EPR with penetration depths of approximately 7 cm and a specially designed partially deuterated nitroxide probe [ 19 , 20 ] for microviscosity studies in a mouse model of cancer. Recently we synthesized 13 C 1 -substituted trityl radical ( 13 C-dFT, Scheme 1 ) [ 21 ] with viscosity-dependent EPR linewidth broadening of about two orders of magnitude higher than that for the nitroxide radical probes [ 17 , 18 , 20 ].…”

Evaluation and Comparison of Pulsed and Continuous Wave Radiofrequency Electron Paramagnetic Resonance Techniques for in Vivo Detection and Imaging of Free Radicals

“…EPR can provide useful pathophysiological and biophysical information because of the capabilities of ESR spectra to reflect the environmental conditions. For example, it is possible to study the tissue metabolic redox state (50), to monitor pO 2 in normal and tumor tissues (43) and to measure tissue pH and viscosity (7). Also, short-lived radical species can be detected indirectly by in vivo spin trapping (51).…”

“…The sensitivity of EPR spectral properties (hyperfine splitting, linewidth) to physiological parameters such as pH, pO 2 , and viscosity makes EPR imaging a potential functional imaging technique (7 ). EPR imaging systems for in vivo applications are designed to operate in the low-frequency region , where the dielectric loss is minimal (8)(9)(10)(11)(12)(13)(14).…”

Photolithographic production of glass sample holders for improved sensitivity and resolution in ESR microscopy

“…In many of these applications, ESRM could provide information complementary to that obtained by more common techniques such as fluorescence and atomic force microscopy. For example, ESR can be used to accurately map 0 2 concentration [2,9], reveal chemical specific information about reactive oxygen and nitrogen species [10][11][12], measure and image microviscosity [13], pH [14], and redox state [15]. All these parameters of interest were already measured with conventional "spectroscopic" ESR, as well as with large-scale ESR imaging machines and could therefore be acquired by ESRM measurements.…”