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Diminished Aqueous Microviscosity of Tumors in Murine Models Measured with in Vivo Radiofrequency Electron Paramagnetic Resonance¹

Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637 [H. J. H., G. V. R. C., E. D. B., C. Y., M. P., D. J. G.], and the Dana-Farber Cancer Institute, Boston, Massachusetts 02115 [B. A. T.]

Using very low frequency in vivo electron paramagnetic resonance (EPR), we have compared, for the first time, the average microviscosity of the total aqueous compartment of murine fibrosarcomas and that of normal leg tissue in a living animal. EPR spectra from dissolved nitroxide spin probes report the solvent microviscosity. The tumor aqueous microviscosity, 1.8 ± 0.1 centipoise, was significantly lower than that of the corresponding normal tissue, 2.9 ± 0.3 centipoise, a difference of 38 ± 7%. These results confirm the commonly observed increase in the water proton transverse relaxation times (T₂) in magnetic resonance imaging of hyperproliferative states, for example, malignancy. The specificity of the localization of the EPR signal indicates a substantial portion of the T₂ increase seen in magnetic resonance imaging derives from decreased bulk-water viscosity. The effect of this microviscosity differences may be the basis of several physiological differences between tumors and normal tissues which could confer a growth rate advantage to tumor tissue.

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