Correlations between in vivo 31P MRS measurements, tumor size, cell survival, and hypoxic fraction in the murine EMT6 tumor.

Abstract

Phosphorus metabolite ratios were measured using 31P magnetic resonance spectroscopy shortly before measurement of cell survival and radiobiologic hypoxic fraction (HF) in EMT6/SF tumors, transplanted into a hindlimb of Balb/c mice. A total of 58 tumors with a volume range of 180 to 1250 mm3 were examined in experiments entailing no anesthesia. Postirradiation tumor cell viability was measured using an in vitro clonogenic assay. Correlations between tumor volume, surviving fraction (SF), HF, phosphorus metabolite ratios, and intracellular pH were computed. Both SF and HF increased significantly with tumor volume as did the metabolite ratios of inorganic phosphorus and phosphomonoesters to nucleoside triphosphates (Pi/NTP and PME/NTP, respectively), as well as Pi to phosphocreatine (Pi/PCr). In comparison to HF, the ratios of Pi/NTP, Pi/PCr, and PME/NTP each yielded significant positive correlations (Kendall correlation coefficients(tau) = 0.25 to 0.33). However, these were not significantly stronger than the correlation between HF and volume (tau = 0.21). Apparent values of tumor pH did not correlate with any other measured parameter. While these results indicate a statistical relationship between HF and the measured metabolite ratios, the widely scattered data, as reflected by magnitude of tau less than 0.35, made metabolite ratios poor predictors of HF in individual tumors.