Effects of motexafin gadolinium on tumor metabolism and radiation sensitivity

Purpose: Experiments were undertaken to determine if metabolic changes induced by Motexafin gadolinium (Gd-Tex(+2), XCYTRIN) predict time intervals between drug and radiation wherein there is enhancement of radiation efficacy. Methods and Materials: We evaluated the effect of Gd-Tex(+2) on tumor metabolism and on tumor growth using a mouse mammary carcinoma model and P-31 nuclear magnetic resonance (NMR) experiments. Response to therapy was evaluated based on time for the tumor to regrow to pretreatment size and also tumor doubling time. Results: P-31 NMR experiments indicated that Gd-Tex(+2) effected tumor energy metabolism during the first 24 hours postadministration. A decrease in phosphocreatine was noted at 2 (p < 0.04), 6 (p < 0.006), and 24 (p < 0.001) hours post Gd-Tex(+2). A decrease in nucleoside triphosphates was noted only at 2 hours (p < 0.02), with subsequent recovery at 6 hours. Phosphocreatine in control (saline treated) tumors showed a significant decrease only at 24 hours (p < 0.01). Irradiation at 2 and 6 hours post Gd-Tex(+2) induced an enhanced effect compared to radiation alone as measured by analyzing the growth curves, maximum tumor volumes, and the time for the tumors to regrow to their initial volumes. Irradiation at 24 hours post Gd-Tex(+2) induced a modest enhancement in tumor growth delay compared to radiation alone. Discussion: NMR spectroscopy may be useful for monitoring tumor metabolism after treatment with Gd-Tex(+2) and administering radiation during the time of maximal efficacy of Gd-Tex(+2). <(c)> 2001 Elsevier Science Inc.