EVALUATION OF LACTATE AS A H-1 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY INDEX FOR NONINVASIVE PREDICTION AND EARLY DETECTION OF TUMOR RESPONSE TO RADIATION-THERAPY IN EMT6 TUMORS

In a recent study (Inf. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 199 6), H-1 nuclear magnetic resonance (NMR) spectroscopy was used to demo nstrate significant decreases in lactate levels after gamma irradiatio n of radiosensitive RIF-1 tumors in vitro. For comparison, we have exa mined the effects of gamma radiation on lactate levels in the more rad ioresistant EMT6 tumor. Single-slice (5-6 mm thick) localized H-1 spec tra of subcutaneous RIF-1 (untreated) and EMT6 tumors (pretreatment, 2 4 and 48 h postirradiation with 4, 10 or 20 Gy of gamma radiation) wer e measured by the selective multiple quantum coherence transfer method (Sel-MQC, -4 min acquisition time). Both pretreatment lactate levels and pretreatment lactate dehydrogenase (LDH) activities were found to be similar in RIF-1 and EMT6 tumors, suggesting that steady-state lact ate levels are unlikely to be reliable indices for predicting response to radiation therapy. After 10 Gy gamma irradiation, EMT6 tumors show ed a 21% decrease relative to pretreatment lactate levels at 48 h (1.0 4 +/- 0.22 to 0.82 +/- 0.16; P = 0.06); after 20 Gy a 40% decrease was observed at 48 h (1.34 +/- 0.27 to 0.81 +/- ct 0.10; P = 0.07). No si gnificant changes in lactate levels were observed in control EMT6 tumo rs or in tumors treated with 4 Gy of gamma radiation, in contrast to c hanges detected previously in RIF-1 tumors, which showed a significant decrease in lactate by 48 h for both 2 and 4 Gy, The decreased effect of radiation on lactate levels in EMT6 compared to RIF-I tumors may b e attributed to the higher hypoxic fraction and lower radiosensitivity of EMT6 tumors (Int. J. Radiat. Oncol. Biol. Phys. 10, 695-712, 1984) . The decrease in lactate levels did not, however, strictly reflect th e extent of the response to therapy for the high dose of 20 Gy. This s tudy together with our earlier study (Int. J. Radiat, Oncol. Biol. Phy s. 36, 635-639, 1996) provides evidence to support the hypothesis that changes in steady-state tumor lactate levels may serve as sensitive e arly indices of tumor response to gamma radiation at doses of the orde r of 2 to 4 Gy, (C) 1998 by Radiation Research Society.