31P magnetic resonance spectroscopy is sensitive to tumor hypoxia: perfusion and oxygenation of rat 9L gliosarcoma after treatment with BCNU.

The mechanism behind the relative increase in high-energy phosphates observed by MRS in many tumors following chemotherapy is poorly understood. To test the hypothesis that this metabolic activation is associated with a decrease in tumor hypoxia, tumor blood flow and oxygenation were measured in tumors that were also analyzed by MRS. 31P MR spectra were acquired with a GE 2T CSI spectrometer from subcutaneous 9L tumors in rats 4 days following treatment with BCNU (10 mg/kg) and from age-matched sham-treated control tumors. BCNU-treated tumors (n = 13) underwent a significant improvement in bioenergetic state compared to control tumors (n = 14), showing a relative increase in high-energy phosphate (Pi/phosphocreatine) (p less than 0.01), and a relative decrease in Pi (Pi/alpha nucleoside biphosphate) (p less than 0.01). Gamma camera imaging of 133Xe washout, following injection of 133Xe in saline into control and treated 9L tumors 4 days after treatment, was used to measure tumor perfusion. Sham-treated control tumors (n = 21) were perfused at a rate of 35.4 (+/- 6.4 SE) mL/100 g/min, while BCNU-treated tumors (n = 20) were perfused at a rate of 55.1 (+/- 7.5 SE) mL/100 g/min (T = 1.96; p less than 0.05). The partial pressure of oxygen (pO2), measured with a polarographic electrode was found to be significantly higher in treated 9L than in sham-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)