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Therapeutic efficacy as predicted by quantitative assessment of murine RIF-1 tumour pH and phosphorous metabolite response during hyperthermia: an in vivo 31P NMR study
Authors:T. Bezabeh  J. L. Evelhoch  P. Thompson  D. J. Sloop  J. J. H. Ackerman
Affiliation:1. Department of Chemistry, Campus Box 1134, Washington University, One Brookings Drive, St. Louis, Missouri 63130-4899, USA;2. Institute for Biodiagnostics, National Research Council, Winnipeg, Manitoba R3B 1Y6, Canadaackerman@wustl.edu;4. Division of Hematology and Oncology, Department of Internal Medicine, Wayne State University, School of Medicine, Detroit, Michigan 48201-2097, USA;5. World Wide Clinical Technology, Pfizer Global Research and Development, Mail Stop: 50-M129, 2800 Plymouth Road, Ann Arbor, MI 48105, USA;6. Washington University School of Medicine, 660 South Euclid, St. Louis, Missouri 63110-1039, USA;7. Washington University School of Medicine, 660 South Euclid, St. Louis, Missouri 63110-1039, USA
Abstract:Described herein are the initial findings from an ‘in-magnet’ 31P NMR compatible hyperthermia system capable of concurrently heating and monitoring the metabolic response of murine tumours; the murine radiation induced fibrosarcoma (RIF-1) was employed for these studies. At thermal doses sufficient to raise tumour temperature to 41.5 and 43°C for a period of 30?min, a marked and rapid decrease in nucleoside triphosphate concentration and in pH was observed during the heating period, while inorganic phosphate concentration increased significantly but more gradually. These 31P NMR determined metabolic indices remained depressed/elevated throughout a 1.5?h post-hyperthermia monitoring period. Importantly, these metabolic indices correlated significantly with specific growth delay. This suggests a possible role for NMR spectroscopy in early assessment, and perhaps control, of therapeutic response to hyperthermia.
Keywords:Thermal dose  specific growth delay  surviving fraction  Bayesian analysis  therapeutic response
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