METABOLIC ALTERATIONS IN IMPLANTED HUMAN TUMORS AFTER COMBINED RADIATION AND HYPERTHERIMIA THERAPY MEASURED BY IN-VIVO P-31 MRS

The bioenergetics of human lung tumors grown subcutaneously in KSN nud e mice, were studied in vivo using P-31 NMR spectroscopy up to 27 days following radiotherapy and/or hyperthermia. Six tumors were treated w ith radiation (20 Gy, single fraction) and hyperthermia (44 degrees C, 10 min). There was a significant increase in the ratio of inorganic p hosphate to beta-nucleoside triphosphate (Pi/beta-NTP) 24 h after radi ation plus hyperthermia (p <.01), but a significant decrease 6 days af ter the treatment (p <.05) relative to untreated controls. Furthermore , the combined therapy produce significant acidosis at 24 h post thera py followed by significant alkalosis at 6 days compared to no treatmen t. This biphasic pattern was also significant in comparison with the p retreatment values of Pi/beta-NTP and pH. The combined therapy produce d not only tumor decline at 24 h indicated by increased Pi/beta-NTP ra tio and acidic pH shift, but also metabolic activation of tumor cells at 6 days indicated by decreased Pi/beta-NTP ratio and alkalotic pH sh ift. The tumor blood flow estimated by hydrogen ion clearance curves w ere completely depleted at 24 h and fully recovered to pretreatment le vel 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 perfus ion status. The P-31 spectra of tumors following the combined therapy were concluded to demonstrate additive physiological effects of hypert hermia and radiation.