Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biological systems.

Abstract

Lithium phthalocyanine (LiPc) is a prototype of another generation of synthetic, metallic-organic, paramagnetic crystallites that appear very useful for in vitro and in vivo electron paramagnetic resonance oximetry. The peak-to-peak line width of the electron paramagnetic resonance spectrum of LiPc is a linear function ofthe partial pressure ofoxygen (PO2); this linear relation is independent of the medium surrounding the LiPc. It has an extremely exchange-narrowed spectrum (peak-to-peak line width = 14 mG in the absence of 02). Physicochemically LiPc is very stable; its response to pO2 does not change with conditions and environments (e.g., pH, temperature, redox conditions) likely to occur in viable biological systems. These characteristics provide the sensitivity, accuracy, and range to measure physiologically and pathologically pertinent 02 tensions (0.1-50 mmHg; 1 mmHg = 133 Pa). The application of LiPc in biological systems is demonstrated in measurements of PO2 in vivo in the heart, brain, and kidney of rats.The purpose of this article is to describe a technology based on electron paramagnetic resonance (EPR or equivalently, electron spin resonance, ESR) that can significantly improve the ability to measure the partial pressure of 02 (PO2) under biologically pertinent conditions in vitro, in vivo, and potentially in human subjects. This article focuses on a prototype ofa class of crystalline paramagnetic probes, lithium phthalocyanine (LiPc), and aims at providing sufficient detail to facilitate the use of these probes in viable biological systems. The critical capabilities of this technology are the ability to measure PO2 at the levels (usually <40 mmHg and can be as low as 0.1 mmHg; 1 mmHg = 133 Pa) and sites (e.g., in tissues in vivo and inside cells) needed to understand biological processes.

The chemistry and biology of nitroxide compounds

“…An extension of this is the use of techniques previously reserved for the laboratory such as EPR imaging which detects unpaired electrons in such species as transition metal complexes and free radicals [39][40][41]. Unpaired electrons are extremely rare in normal tissues, so little if any EPR signal is detected in biological tissues.…”

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

“…This material has an extremely narrow line of around 25-30 mGauss under 0% oxygen; this linewidth broadens proportionally to pO 2 with a linewidth of about 1000 mGauss in air. 167 The linearity of the response (Fig. 2) is especially valuable for measuring dramatic changes in pO 2 : the signal-to-noise ratio is particularly high at low pO 2 due to the narrowness of the linewidth, and the linewidth at high pO 2 remains sufficiently narrow to get a reasonable signal to noise ratio in these conditions.…”

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.…”