H. Lyng et al., P-31-NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY IN-VIVO OF 6 HUMAN-MELANOMA XENOGRAFT LINES - TUMOR BIOENERGETIC STATUS AND BLOOD-SUPPLY, British Journal of Cancer, 68(6), 1993, pp. 1061-1070
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.