Metabolism of tumor regression from angiogenesis inhibition: 31P magnetic resonance spectroscopy

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Abstract
31P NMR spectroscopy was used to analyze the in vivo metabolism of reticulum cell sarcoma of mice. The ratio of high‐ to low‐energy phosphates ATPB/(Pi + PME) was measured to reflect the relative metabolic state in the tumor. Of the 34 mice studied, 26 were treated with an antiangiogenesis regimen of heparin and cortisone. Eighty‐two percent of the tumors treated eventually decreased in volume (P < 0.01 ). Volumes and spectroscopic information of 20 tumors were analyzed. Although the average untreated volume was similar to the volume after 3 days of treatment, the average ATPB/(Pi + PME) ratio rose from 0.34 ± 0.10 to 0.47 + 0.07 (P = 0.02). However, after 6 days of treatment, the volume significantly decreased (P < 0.0001) but the ratio did not significantly rise further (P = 0.06). The rise in the high‐energy phosphate preceded a significant decrease in volume of the tumors. In addition, the replenishment of the high‐energy stores with tumor regression coincided with the histologic findings of a decrease in the number of tumor cells, a decrease of the mitotic index, and a decrease of the number of necrotic cells present with ongoing treatment. Our data suggest that noninvasive methods of assessing early biochemical response of tumor regression may be possible.