In vivo ³¹P NMR spectroscopy of human musculoskeletal tumors as a measure of response to chemotherapy

The value of in vivo ³¹P NMR spectroscopy to provide indicators of response to cytostatic chemotherapy was studied in patients with malignant mosculoskeletal tumors. Characteristics of untreated cancers were strong signals of PME and PDE, moderately increased P_j and low PCr. The intracellular pH was slightly alkaline. The intracellular concentration of free magnesium was 70% of that in muscle. Spectroscopic findings at different times of therapy were compared with the percentage of tumor necrosis after surgical resection in 28 patients. In follow-up studies, energy-rich phosphates declined in nonresponders, while PME, P_j and frequently PDE increased. Treatment response appeared to involve the reversal of these trends. In five responders, a biphasic pattern was observed, i.e. initially the spectrum changed into that of severely ischemic cell injury followed by a successive phase of apparent 'tumor activation'. Pretreatment levels of (PCr+P_j)/total phosphate ≥ 035 and PCr/ α-NTP ≥1.5, an accelerated increase in total low-energy phosphates/total high-energy phosphates (≥3.0%/day) after the initial drug application, and a long-term decrease (≤ -0.4%/day) during later therapy were highly indicative of tumor response to chemotherapy. Such spectroscopic predictors for treatment response proved to be superior to currently used indices such as tumor size.