In Vivo and in vitro EPR oximetry with fusinite: A new coal‐derived, particulate EPR probe

Abstract

The peak-to-peak line width (LW) of the first derivative electron spin resonance (EPR) spectrum of the coal maceral fusinite is reversibly broadened by O2. The extent of broadening per unit of partial pressure of oxygen (pO2) is unusually large, exceeding that of nitroxides by almost two orders of magnitude. This paramagnetic property of fusinite, combined with its very stable physicochemical properties and low toxicity, is shown to be of utility in the measurement of pO2 in vitro and in vivo. Fusinite particles are endocytosed by chinese hamster ovary (CHO) cells in vitro; this is useful for intracellular O2 measurements with commercially available EPR spectrometers operating at 9.1-9.3 GHz. For measurement of oxygen in vivo using low frequency EPR (1.1-1.3 GHz), fusinite provides a sensitive and persistent means to measure pO2 in tissues. Particles implanted into the gastrocnemius muscle of A/J mice remained interstitially in the same position for months with undiminished sensitivity to pO2 and no specific toxic effects.

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

“…The initial studies used fusinite, a coal maceral which is insoluble, amorphous, aromatic, and of organic origin. 172,173 This coal is produced from materials which have burned before becoming fossilized. It is especially useful for measurements from 0 to 20 mmHg.…”

“…43 This technique has already been used in brain, 168-170 heart, 193,207-211 gastrointestinal tract, 194 skeletal muscle, 147,167,[171][172][173][174][175]183 liver, 212-217 kidneys 218 and skin. 181,219,220 However, since oxygenation is of crucial importance in tumors to predict the outcome of a treatment, and since there is hope for manipulating local oxygenation to improve the efficacy of anti-cancer therapies, many efforts have been carried out to apply this technology for the characterization of tumor oxygenation.…”

Cardiac applications of EPR imaging

“…In each case, accurate measurement of oxygeninduced line broadening requires the presence of a suitable EPR probe. In general, particulate probes such as lithium phthalocyanine, [53][54][55][56] naturally occurring coal 57,58 and synthetic char 59 are suitable for measurements of oxygen partial pressure, while soluble probes such as nitroxyls and trityl molecules measure dissolved oxygen concentration.…”

“…Naturally occurring (coals, fusinite), semisynthetic (India ink, sugar chars, carbon blacks) and purely synthetic materials (LiPc) have been reported for EPR oximetry. 57,58,63 Imaging methods-'spatial' and 'spectral-spatial' imaging EPRI can be performed in purely the spatial domain to obtain one-, two-or three-dimensional (1D, 2D or 3D) images of free radical distribution in objects. This usually requires one to three sets of gradient coils.…”

Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR

“…Once particulate materials are implanted in tissue, it is possible to make repeated localized measurements over long periods of time. Recently, several new paramagnetic particulate materials have been found to exhibit a pO 2 -dependent EPR linewidth: lithium phthalocyanine crystals, 13 lithium naphthalocyanine crystals, 14 natural charcoals such as fusinite 15 or gloxy, 16 analytical charcoals, 17,18 and synthetic carbohydrate chars. 19 Another type of particulate material that is particularly interesting can be found in India inks, which are suspensions of carbon black (CB) particles.…”