Metabolic alterations in implanted human tumors after combined radiation and hyperthermia therapy measured by in vivo 31P MRS.
The bioenergetics of human lung tumors grown subcutaneously in KSN nude mice, were studied in vivo using 31P NMR spectroscopy up to 27 days following radiotherapy and/or hyperthermia. Six tumors were treated with radiation (20 Gy, single fraction) and hyperthermia (44 degrees C, 10 min). There was a significant increase in the ratio of inorganic phosphate to beta-nucleoside triphosphate (Pi/beta-NTP) 24 h after radiation plus hyperthermia (p < .01), but a significant decrease 6 days after the treatment (p < .05) relative to untreated controls. Furthermore, the combined therapy produce significant acidosis at 24 h post therapy followed by significant alkalosis at 6 days compared to no treatment. This biphasic pattern was also significant in comparison with the pretreatment values of Pi/beta-NTP and pH. The combined therapy produced not only tumor decline at 24 h indicated by increased Pi/beta-NTP ratio and acidic pH shift, but also metabolic activation of tumor cells at 6 days indicated by decreased Pi/beta-NTP ratio and alkalotic pH shift. The tumor blood flow estimated by hydrogen ion clearance curves were completely depleted at 24 h and fully recovered to pretreatment level at 6 days. Reasonable close negative correlation between the blood flow and Pi/beta-NTP ratio (r = -0.59, p < .01) indicated that the two contrasting physiological states were closely related to tumor perfusion status. The 31P spectra of tumors following the combined therapy were concluded to demonstrate additive physiological effects of hyperthermia and radiation.
Kimura
H
H
Department of Radiology, Fukui Medical School, Japan.
Itoh
S
S
Kawamura
Y
Y
Nakatsugawa
S
S
Ishii
Y
Y
D000818:Animals; D018196:Carcinoma, Adenosquamous / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009711:Nucleotides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009711:Nucleotides; D010710:Phosphates