We examined whether grossly similar tumor responses, obtained by different therapies, induce similar patterns of change in the ratios of nucleotide triphosphate (NTP) to inorganic phosphate (P-i) in two human tumor lines, derived from the tumor of the same patient. The tumor responses were induced by doxorubicin 10 mg/kg i.p. or 5 Gy X-radiation in the human small cell lung cancer (SCLC) lines 54A and 54B, grown as xenografts in athymic nude mice. In vivo P-31 magnetic resonance spectroscopy of tumors was performed pretherapeutically, and on days 1, 4, 8, and 15 following therapy, in a 4.7 T magnet. Individual NTP/P-i ratios were calculated relative to the pretherapeutic values, and treated (n=28) versus controls (n=28) were compared. In both tumor lines, doxorubicin induced a significant drop in NTP/P-i at day 1. In 54A tumors 5 Gy induced a significant increase in NTP/P-i, whereas no difference between the NTP/P-i of irradiated and controls was found in 54B tumors. Thus three distinct NTP/P-i patterns were observed in tumors during response to therapy: (i) A decrease, (ii) an increase, and (iii) no change. Our findings indicate that changes in this ratio do not correlate independently with tumor response in the SCLC sublines 54A and 54B.

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