P-31-NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY IN-VIVO OF 6 HUMAN-MELANOMA XENOGRAFT LINES - TUMOR BIOENERGETIC STATUS AND BLOOD-SUPPLY

Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice wer esubjected to P-31-nuclear magnetic resonance (P-31-NMR) spectroscopy in vivo. The following resonances were detected: phosphomonoesters (PM E), inorganic phosphate (P(i)), phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma, alpha and beta (NTPgamma, al pha and beta). The main purpose of the work was to search for possible relationships between P-31-NMR resonance ratios and tumour pH on the one hand and blood supply per viable tumour cell on the other. The lat ter parameter was measured by using the Rb-86 uptake method. Tumour bi oenergetic status [the (PCr + NTPbeta)/P(i) resonance ratio], tumour p H and blood supply per viable tumour cell decreased with increasing tu mour volume for five of the six xenograft lines. The decrease in tumou r bioenergetic status was due to a decrease in the (PCr + NTPbeta)/tot al resonance ratio as well as an increase in the P(i)/total resonance ratio. The decrease in the (PCr + NTPbeta)/total resonance ratio was m ainly a consequence of a decrease in the PCr/total resonance ratio for two lines and mainly a consequence of a decrease in the NTPbeta/total resonance ratio for three lines. The magnitude of the decrease in the (PCr + NTPbeta)/total resonance ratio and the magnitude of the decrea se in tumour pH were correlated to the magnitude of the decrease in bl ood supply per viable tumour cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the magnitude of this decrease was la rger for the tumour lines showing a high than for those showing a low blood supply per viable tumour cell. No correlations across the tumour lines were found between tumour pH and tumour bioenergetic status or any other resonance ratio on the one hand and blood supply per viable tumour cell on the other. The differences in the P-31-NMR spectrum bet ween the tumour lines were probably caused by differences in the intri nsic biochemical properties of the tumour cells rather than by the dif ferences in blood supply per viable tumour cell. Biochemical propertie s of particular importance included rate of respiration, glycolytic ca pacity and tolerance to hypoxic stress. On the other hand, tumour bioe nergetic status and tumour pH were correlated to blood supply per viab le tumour cell within individual tumour lines. These observations sugg est that P-31-NMR spectroscopy may be developed to be a clinically use ful method for monitoring tumour blood supply and parameters related t o tumour blood supply during and after physiological intervention and tumour treatment. However, clinically useful parameters for prediction of tumour treatment resistance caused by insufficient blood supply ca n probably not be derived from a single P-31-NMR spectrum since correl ations across tumour lines were not detected; additional information i s needed.