Figure 3.

Pharmacokinetics of nitroxide in normal muscle and tumor tissues. Time course of the EPR signal intensity of 3-CP in the normal leg muscle and tumor tissue of RIF-1 tumor-bearing mice, infused (i.v.) with a saline solution of 3-CP, were obtained by double integration of the spectra. A) The semilog plot shows the clearance of the nitroxide (in arbitrary units) as a function of time in the normal muscle and tumor tissue of untreated tumor-bearing mice and in the tumor tissue of mice treated (i.p.) with BSO (2.25 mmol/kg) 6 h before the measurements. The solid lines through the data points are linear fit to the respective data set, which suggests compliance with a pseudo first-order rate law. B) Bar-graph showing the measured pseudo first-order rate constants of nitroxide reduction in the tissues. The data represent mean ± SE of measurements on three to five mice per group. The rate constants were: untreated normal muscle, 0.037 ± 0.005 min⁻¹; untreated tumor, 0.063 ± 0.008 min⁻¹, and BSO-treated tumor, 0.052 ± 0.006 min⁻¹. *, significantly different from normal muscle; **, significantly different from untreated RIF-1 tissue. C) Spatially resolved clearance of nitroxide in RIF-1 tumor tissue. After tail vein infusion of 3-CP, a series of two-dimensional images of the nitroxide from tumor (untreated and BSO-treated) were measured using L-band EPRI method. A few selected images and the corresponding approximate time after infusion are shown. The images represent the mean nitroxide concentration in a two-dimensional projection of the tissue volume (10 × 10 mm²; depth, 5 mm) averaged over 1.5–2.0 min. The image data were acquired using a magnetic field gradient of 15 G/cm at 16 orientations in the two-dimensional plane. Each image within a series was normalized with respect to the maximum intensity in that series. The nitroxide in the tumor of BSO-treated mouse persisted longer, compared with that in the untreated mouse. (Adapted with permission from reference Kuppusamy et al 2002)