The effects of
chemotherapy [25 mg/kg
1,3-bis(2-chloroethyl)-1-nitrosourea administered with a single i.p. injection] on cellular energetics by 31P nuclear magnetic resonance (NMR) spectroscopy, total tissue
sodium by single-quantum (SQ) 23Na NMR spectroscopy, and intracellular
sodium by triple-quantum-filtered (TQF) 23Na NMR spectroscopy were studied in the s.c. 9L
glioma. Animals were studied by NMR 2 days before
therapy and 1 and 5 days after
therapy. Destructive chemical analysis was also performed 5 days after
therapy to validate the origin of changes in SQ and TQF 23Na signals. One day
after treatment, there was no significant difference between control and treated
tumors in terms of
tumor size or 23Na and 31P spectral data. Five days after
therapy, treated
tumors had 28 +/- 16% (P < 0.1) lower SQ 23Na signal intensity, 46 +/- 20% (P < 0.05) lower TQF 23Na signal intensity, 125 +/- 51% (P < 0.05) higher
ATP:Pi ratio, 186 +/- 69% (P < 0.05) higher
phosphocreatine:Pi ratio, and 0.17 +/- 0.06 pH units (P < 0.05) higher intracellular pH compared with control
tumors. No significant differences in TQF 23Na relaxation times were seen between control and treated
tumors at any time point. Destructive chemical analysis showed that the relative extracellular space of control and treated
tumors was identical, but the treated
tumors had 21 +/- 8% (P < 0.05) lower total tissue Na+ concentration and 60 +/- 24% (P < 0.05) lower intracellular Na+ concentration compared with the controls. The higher
phosphocreatine:Pi and
ATP:Pi ratios after
1,3-bis(2-chloroethyl)-1-nitrosourea treatment indicate improved bioenergetic status in the surviving
tumor cells. The decrease in SQ and multiple-quantum-filtered 23Na signal intensity was largely attributable to a decrease in Na(i)+ because the treatment did not change the relative extracellular space. The improved energy metabolism could decrease the intracellular concentration of Na+ by increasing the activity of Na+-K+-
ATPase and decreasing the activity of Na+/H+. Although both 23Na and 31P spectra were consistent with improved cellular metabolism in treated
tumors, the 23Na methods may be better suited for monitoring response to
therapy because of higher signal:noise ratio and ease of imaging the single 23Na resonance.