Murine Mammary Tumor Response to Hyperthermia and Radiotherapy Evaluated by in Vivo ³¹P-Nuclear Magnetic Resonance Spectroscopy¹

The response of the s.c.-implanted murine mammary carcinoma NU-82 to hyperthermia was followed as a function of time by ³¹P-nuclear magnetic resonance spectroscopy. Treatment consisted of elevation of the temperature of the tumors to 41–45°C during 15 min. At 18 h after temperatures of up to 42, 43, 44, and 45°C the ratio of ATP/P_i was unchanged, decreased, largely decreased, and approaching zero, respectively. After the higher doses the relative concentrations (in percentage of total phosphate as visible in the nuclear magnetic resonance spectrum) of phosphomonoesters (mainly phosphoethanolamine) and phosphocreatine also decreased in favor of P_i. The changes in phosphodiesters (mainly glycerophosphocholine) correlated linearly with the changes in ATP (r = 0.84, P < 0.025). Whereas the limited spectral changes after a dose of 43°C were nullified within 24 h, the more drastic changes after a dose of 45°C lasted at least 8 days. The heavier dose not only induced temporary decreases in tumor perfusion like the lower dose (phase 1) but subsequently, unlike the lower dose, resulted in formation of necrosis (phase 2). In the same tumor we found increases in P_i and decreases in ATP and phosphodiesters after radiotherapy with a dose of 20 Gy. Radiotherapy (20 Gy) combined with hyperthermia (44°C) appeared to strengthen these effects and resulted in an improved tumor response (regression).