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H Lyng

Publications and source records attributed to H Lyng.

At least 37 records · Page 2Linked to original sources

Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia.

BACKGROUND AND PURPOSE: The use of polarographic needle electrodes for measurement of oxygen tension (pO2) in tumours requires documentation of the validity of the method. In the present work the pO2 values measured polarographically with the Eppendorf pO2 histograph in human tumours were compared with the histological appearance of the tumour tissue, i.e. vascular density, fraction of necrosis and fraction of hypoxic tissue, to investigate whether the measurements reflected the expected pO2. MATERIALS AND METHODS: The pO2 was measured in cervix tumours in patients and in human melanoma xenografted tumours in athymic mice. Vascular density was determined in the cervix tumours by histological analysis of biopsies from the pO2 measurement tracks. Fraction of necrosis and fraction of hypoxic tissue, i.e. tissue binding the hypoxia marker pimonidazole, were determined in the melanomas by analysis of histological sections from the tumour planes in which the pO2 measurements were performed. RESULTS: The pO2 distributions showed large intratumour heterogeneity. In cervix tumours, tumour regions with vascular density (vascular length per unit tissue volume) in the range of 47-77 mm/mm3 showed higher pO2 than tumour regions with vascular density in the range of 20-47 mm/mm3, which in turn showed higher pO2 than tumour regions with vascular density in the range of 0-20 mm/mm3. In melanomas, tumour regions in which necrosis and hypoxia constituted more than 50% of the tissue showed lower pO2 than other tumour regions. CONCLUSIONS: The pO2 measured in the tumours was consistent with the histological appearance of the tissue in which the measurements were performed, suggesting that reliable pO2 distributions of tumours can be obtained with polarographic needle electrodes.

Adult↗

Proton relaxation times and interstitial fluid pressure in human melanoma xenografts.

The interstitial fluid pressure (IFP) and the proton spin-lattice and spin-spin relaxation times (T1 and T2) of some experimental tumours have been shown to be related to tumour water content. These observations have led to the hypothesis that magnetic resonance imaging (MRI) might be a clinically useful non-invasive method for assessment of tumour IFP. The purpose of the work reported here was to examine the general validity of this hypothesis. R-18 human melanoma xenografts grown intradermally in Balb/c nu/nu mice were used as the tumour model system. Median T1 and T2 were determined by spin-echo MRI using a 1.5-T clinical whole-body tomograph. IFP was measured using the wick-in-needle technique. No correlation was found between tumour IFP and fractional tumour water content. Moreover, there was no correlation between median T1 or T2 and IFP, suggesting that proton T1 and T2 values determined by MRI cannot be used clinically to assess tumour IFP and thereby to predict the uptake of macromolecular therapeutic agents.

Animals↗

Correlation of high lactate levels in head and neck tumors with incidence of metastasis.

Using quantitative bioluminescence imaging, tissue concentrations of ATP, glucose, and lactate were registered in biopsies that were taken from primary tumors of human head and neck at the time of first cancer diagnosis. From 15 patients investigated at present, 6 had locoregional lymph node metastasis, 6 had no detectable metastatic spread, 2 biopsies contained dysplasias, and 1 biopsy consisted exclusively of normal mucosal and submucosal tissue. There was no correlation between staging or grading and any of the metabolic parameters measured. Mean lactate concentrations (+/-SD) were significantly higher and scattered over a wider range in tumors with metastatic spread (12.3 +/- 3.3 mumol/g) in comparison with malignancies in patients without metastasis (4.7 +/- 1.5 mumol/g). Despite the low number of patients, these differences were statistically highly significant (P < 0.005; Mann-Whitney). Neither ATP nor glucose contents showed such a correlation with the emergence of metastasis. Mean lactate contents of the two dysplasias were 0.1 and 3.5 mumol/g; that of the normal tissue was 0.1 mumol/g. Although these findings have to be verified in a higher number of patients, the present data indicate that elevated lactate levels in primary tumors of head and neck may be associated with a high risk of metastatic spread. With the underlying mechanisms remaining to the investigated, lactate imaging is possibly useful as an early indicator of the malignant potential of tumors in patients.

Aged↗

Xenograft model systems for human melanoma.

Human melanoma cells inoculated intradermally into congenitally immune-deficient mice initiate angiogenesis and give rise to tumors with a human parenchyma and a murine stroma. These tumors are similar to the donor patients' tumors with respect to histological appearance, karyotype and molecular pathology. The cellular treatment sensitivities and the organ-specific metastatic patterns of the donor patients' tumors are also retained after xenotransplantation. Consequently, human melanoma xenografts are exciting experimental models that show great promise for future studies of the molecular biology, angiogenesis, pathophysiology, treatment sensitivity and metastatic behavior of malignant melanoma.

Animals↗

Oxygen tension and vascular density in human cervix carcinoma.

Hypoxia-induced radiation resistance has been proposed to be a consequence of low vascular density in tumours. The purpose of the study reported here was to investigate possible relationships between pretreatment oxygen tension (pO2) and vascular density in patients with cervix carcinoma. Tumour pO2 was measured by the use of polarographic needle electrodes. Biopsies were taken from the electrode tracks and vascular density and tissue composition, i.e. volume fraction of carcinoma tissue, stroma and necrosis, were determined by stereological analysis. The vascular density of individual biopsies was related to the median pO2 of the corresponding electrode track. Tumour regions with vascular density below 24 mm mm(-3) always showed low pO2, whereas tumour areas with vascular density above 24 mm mm(-3) could show a high or a low pO2. This indicates the existence of a threshold value of about 24 mm mm(-3) for vascular density in cervix carcinoma; a vascular density above this value is probably needed before high pO2 can occur. Low vascular density might, therefore, be a useful predictor of hypoxia-induced radiation resistance in cervix carcinoma. High vascular density, on the other hand, can probably not be used to exclude radiation resistance. The differences in pO2 among tumour regions with high vascular density were not a consequence of differences in the amount of necrosis or stroma or in the haemoglobin concentration in peripheral blood of the patients. Model calculations indicated that these differences in pO2 could be explained by differences in the oxygen delivery alone and by differences in the oxygen consumption rate alone.

Biopsy↗

Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: a study of human melanoma multicellular spheroids.

The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia- induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WIX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-microM spheroids were 32 +/- 12% (BEX-c) and 2.5 +/- 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 +/- 6% (BEX-c) and 1.4 +/- 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c showed lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of radiobiologically hypoxic cells in multicellular spheroids.

Apoptosis↗

Hypoxia-induced tetraploidisation of a diploid human melanoma cell line in vitro.

Many human tumours are hyperdiploid, particularly in advanced stages of growth. The purpose of the present work was to investigate whether exposure to hypoxia followed by reoxygenation might induce hyperploidisation of diploid human tumour cells in vitro. The investigation was performed by using the diploid melanoma cell line BEX-c (median chromosome number, 46; DNA index, 1.10 +/- 0.04) as test line and the hyperdiploid melanoma cell line SAX-c (median chromosome number, 61; DNA index, 1.42 +/- 0.03) as control line. Cell cultures kept in glass dishes in air-tight steel chambers were exposed to hypoxia (O2 concentrations < 10 p.p.m. or < 100 p.p.m.) at 37 degrees C for 24 h. DNA content was measured by flow cytometry. Metaphase spreads banded with trypsin-Versene-Giemsa were examined to determine the number of chromosomes per cell. An electronic particle counter was used to measure cell volume. The expression of p53 and pRb was studied by Western blot analysis. Transient exposure to hypoxia was found to induce a doubling of the number of chromosomes in BEX-c but not in SAX-c. The fraction of the BEX-c metaphase spreads with 92 chromosomes was approximately 10% at 18 h after reoxygenation, decreased to approximately 2% at 7 days after reoxygenation and then increased gradually with time. The whole cell population became tetraploid within 25 weeks. BEX-c and SAX-c behaved differently during the 24 h hypoxia exposure. Cell volume and fraction of cells in G2 + M increased with time in BEX-c but remained essentially unchanged in SAX-c. On the other hand, the expression of p53 and pRb was similar for the two lines; hypoxia induced increased expression of p53 and hypophosphorylation of pRb.

Cell Hypoxia↗

Interstitial fluid pressure, perfusion rate and oxygen tension in human melanoma xenografts.

Interstitial fluid pressure (IFP) has been reported to be inversely correlated to rate of perfusion and oxygen tension (pO2) in experimental tumours (Lee et al., 1992; Roh et al., 1991 a). Studies of patients with squamous cell carcinoma of the uterine cervix have provided clinical data consistent with the experimental data (Roh et al., 1991b; Milosevic et al., 1995). These observations have led to the hypothesis that IFP might be a useful indicator of tumour oxygenation status. The purpose of the work reported here was to examine in detail the general validity of this hypothesis. R-18 human melanoma xenografts grown intradermally in Balb/c nu/nu mice were used as tumour model system. IFP and perfusion rate or IFP and pO2 were measured in the same individual tumours in two independent series of experiments. The wick-in-needle method was used to record IFP. Perfusion rate was studied by using the 86Rb uptake method. The KIMOC-6650 Eppendorf histograph was used to measure pO2. IFP, perfusion rate and pO2 differed considerably between individual tumours. However, there was no relationship between IFP and perfusion rate or IFP and pO2, suggesting that the oxygenation status of tumours cannot be derived from measurements of IFP. Consequently, IFP is probably not a useful predictor of radiation resistance caused by hypoxia.

Animals↗

31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation.

The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

MRI of human tumor xenografts in vivo: proton relaxation times and extracellular tumor volume.

Proton T1 and T2 differ substantially between tumors, but the tumor properties causing heterogeneity in T1 and T2 have not been fully recognized. The purpose of the study reported here was to investigate whether differences in T1 and T2 between tumors are mainly a consequence of differences in the fractional volume of the extracellular compartment. The study was performed using a single human tumor xenograft line showing large naturally occurring intratumor heterogeneity in the size of the extracellular compartment. The size of the extracellular compartment was calculated from the volume and the density of the tumor cells. Cell volume was measured by an electronic particle counter. Cell density was determined by stereological analysis of histological preparations. T1 and T2 were measured by MRI in vivo both in the absence and presence of Gd-DTPA. Two spin-echo pulse sequences were used, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60, and 80 ms and the other with a TR of 2,000 ms and TEs of 20, 40, 60, and 80 ms. Measurements of T1 and T2 in the presence of Gd-DTPA were performed in a state of semi-equilibrium between uptake and clearance of Gd-DTPA. MR-images and histological preparations of tumor subregions homogeneous in extracellular volume were analysed in pairs. The extracellular volume differed between tumor subregions from 5 to 70%. T1 and T2 measured in the absence of Gd-DTPA differed between tumor subregions by a factor of approximately 1.5 and increased with increasing extracellular volume. The relative decrease in T1 caused by Gd-DTPA, represented by (T1 control-T1 Gd-DTPA)/T1 control, also increased with increasing extracellular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of melanin on phosphorus T1S in human melanoma xenografts studied by 31P MRS.

31P MRS resonance ratios of tumors depend on the T1S of the phosphorus compounds. The objective of the 31P MRS study reported here was to investigate whether the phosphorus T1S of melanomas are influenced by the presence of melanin. One amelanotic (COX-t) and one melanotic (ROX-t) human melanoma xenograft line were studied at two different tumor volumes: 200 and 1000 mm3. 31P MRS was performed in nonanaesthetized mice at 4.7 T. The T1S were measured by using the superfast inversion recovery technique. Fraction of necrotic tissue in the tumors was determined by histological examination. The ROX-t tumors showed shorter T1S than the COX-t tumors at a volume of 200 mm3, where the fraction of necrotic tissue in the tumors was insignificant. The difference was similar in magnitude for all resonances. The T1S were not significantly different for COX-t and ROX-t at a volume of 1000 mm3, where the tumors of both lines had developed significant necrosis. The phosphorus T1S of melanomas without necrosis can be shortened significantly by the presence of melanin. The magnitude of the T1 shortening is similar for all major compounds. 31P MRS resonance ratios of melanomas are not altered significantly by correcting for effects of partial saturation.

Animals↗

Detection of necrosis in human tumour xenografts by proton magnetic resonance imaging.

Tumours with necrotic regions have an inadequate blood supply and are expected to differ from well-vascularised tumours in response to treatment. The purpose of the present work was to investigate whether proton magnetic resonance imaging (MRI) might be used to detect necrotic regions in tumours. MR images and histological sections from individual tumours of three different amelanotic human melanoma xenograft lines (BEX-t, HUX-t, SAX-t) were analysed in pairs. MRI was performed at 1.5 T using two spin-echo pulse sequences, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60 and 80 ms and the other with a TR of 2000 ms and TEs of 20, 40, 60 and 80 ms. Spin-lattice relaxation time (T1), spin-spin relaxation time (T2) and proton density (N0) were calculated for each volume element corresponding to a pixel. Synthetic MR images, pure T1, T2 and N0 images and spin-echo images with chosen values for TR and TE were generated from these data. T1, T2 and N0 distributions of tumour subregions, corresponding to necrotic regions and regions of viable tissue as defined by histological criteria, were also generated. T1 and T2 were significantly shorter in the necrotic regions than in the regions of viable tissue in all tumours. These differences were sufficiently large to allow the generation of synthetic spin-echo images showing clear contrast between necrosis and viable tissue. Maximum contrast was achieved with TRs within the range 2800-4000 ms and TEs within the range 160-200 ms. Necrotic tissue could also be distinguished from viable tissue in pure T1 and T2 images. Consequently, the possibility exists that MRI might be used for detection of necrotic regions in tumours and hence for prediction of tumour treatment response.

Animals↗

Spin-lattice relaxation time of inorganic phosphate in human tumor xenografts measured in vivo by 31P-magnetic resonance spectroscopy. Influence of oxygen tension.

Previous 31P-magnetic resonance spectroscopy (31P-MRS) studies have suggested that the spin-lattice relaxation time (T1) of the inorganic phosphate (Pi) resonance is shorter in well-oxygenated than in poorly oxygenated tumors. Amelanotic human melanoma xenografts were therefore subjected to 31P-MRS to investigate whether the T1 of the Pi resonance might be a useful parameter for assessment of tumor oxygenation status. It was searched for possible correlations between the T1 of the Pi resonance and oxygen tension or parameters closely related to oxygen tension, including 31P-MRS tumor energy status and blood supply per viable tumor cell. Oxygen tension, tumor energy status, and blood supply per viable tumor cell decreased with increasing tumor volume. In contrast to previous suggestions, the T1 of the Pi resonance decreased with increasing tumor volume and decreasing oxygen tension, tumor energy status, and blood supply per viable tumor cell, possibly because the tumors developed necrotic regions concomitantly with the decrease in oxygenation status, resulting in increased concentrations of freely dissolved para-magnetic ions in the tissue. Consequently, the T1 of the Pi resonance can probably not be utilized to estimate the oxygenation status of tumors, at least not in tumors with necrotic regions.

Animals↗

31P-nuclear magnetic resonance spectroscopy in vivo of four human melanoma xenograft lines: spin-lattice relaxation times.

Phosphorus spin-lattice relaxation times (T1s) were measured in vivo by 31P-nuclear magnetic resonance spectroscopy in tumors from four amelanotic human melanoma xenograft lines grown subcutaneously in BALB/c-nu/nu mice. The T1s were analyzed in relation to tumor volume, fractional tumor water content, and fraction of necrotic tumor tissue. The following resonances were studied: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr), and nucleoside triphosphates gamma, alpha, and beta (NTP gamma, alpha, and beta). Two different techniques were used to measure the T1s: superfast inversion recovery (SUFIR) and conventional inversion recovery (IR). The SUFIR and IR methods gave similar results. Tumors in the volume range 100-3000 mm3 were studied. The PME, Pi, PDE, and PCr resonances showed significantly longer T1s than the NTP gamma, alpha, and beta resonances at small tumor volumes. The T1s at small tumor volumes also differed significantly between the tumor lines. The T1s either decreased or remained unchanged with increasing tumor volume; the volume-dependence of the T1s differed significantly between the tumor lines but not between the resonances. Calculations based on the T1s measured here indicated that the errors in PCr/Pi and NTP beta/Pi resonance ratios due to partial saturation can vary with tumor volume but are usually < 20% at a repetition time of 2.0 s and < 15% at a repetition time of 3.0 s. There was no correlation between the T1s and fractional tumor water content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Magnetic resonance imaging of human melanoma xenografts in vivo: proton spin-lattice and spin-spin relaxation times versus fractional tumour water content and fraction of necrotic tumour tissue.

Proton nuclear magnetic resonance (1H-nmr) imaging is used routinely in clinical oncology to provide macroscopic anatomical information, whereas its potential to provide physiological information about tumours is not well explored. To evaluate the potential usefulness of 1H-nmr imaging in the prediction of tumour treatment resistance caused by unfavourable microenvironmental conditions, possible correlations between proton spin-lattice and spin-spin relaxation times (T1 and T2) and physiological parameters of the tumour microenvironment were investigated. Tumours from six human melanoma xenograft lines were included in the study. 1H-nmr imaging was performed at 1.5 T using spin-echo pulse sequences. T1- and T2-distributions were generated from the images. Fractional tumour water content and the fraction of necrotic tumour tissue were measured immediately after 1H-nmr imaging. Significant correlations across tumour lines were found for T1 and T2 versus fractional tumour water content (p < 0.001) as well as for T1 and T2 versus fraction of necrotic tumour tissue (p < 0.05). Tumours with high fractional water contents had high values of T1 and T2, probably caused by free water in the tumour interstitium. Fractional water content is correlated to interstitial fluid pressure in tumours, high interstitial fluid pressure being indicative of high vascular resistance. Tumours with high fractional water contents are thus expected to show regions with radiobiologically hypoxic cells as well as poor intravascular and interstitial transport of many therapeutic agents. T1 and T2 decreased with increasing fraction of necrotic tumour tissue, perhaps because complexed paramagnetic ions were released during development of necrosis. Viable tumour cells adjacent to necrotic regions are usually chronically hypoxic. Tumours with high fractions of necrotic tissue are thus expected to contain significant proportions of radiobiologically hypoxic cells. Consequently, quantitative 1H-nmr imaging has the potential to be developed as an efficient clinical tool in prediction of tumour treatment resistance caused by hypoxia and/or transport barriers for therapeutic agents. However, much work remains to be done before this potential can be adequately evaluated. One problem is that high fractional tumour water contents result in longer T1 and T2 whereas high fractions of necrotic tumour tissue result in shorter T1 and T2; i.e. the two parameters which are indicative of treatment resistance contribute in opposite directions. Another problem is that the correlations for T1 and T2 versus fraction of necrotic tumour tissue are not particularly strong.

Animals↗

Prediction of treatment temperatures in clinical hyperthermia of locally advanced breast carcinoma: the use of contrast enhanced computed tomography.

PURPOSE: Nineteen patients with locally advanced breast carcinoma were subjected to computed tomography examinations prior to thermoradiotherapy. Pre- and postcontrast computed tomography images were obtained, and tumor contrast enhancement was studied in relation to tissue perfusion, PERF, and steady state temperature, TS, in an attempt to develop an assay for prediction of treatment temperatures in clinical hyperthermia of breast carcinoma. METHODS AND MATERIALS: PERF and TS were calculated from temperature data achieved during the first fraction of the heat treatment regimen. The computed tomography images were subjected to image analysis, and two parameters representing tumor contrast enhancement were calculated from the computed tomography numbers; the absolute increase in mean attenuation, delta N, and the fraction of the postcontrast attenuation values that was higher than the mean precontrast attenuation value, F+C. RESULTS: delta N and F+C were clearly correlated to each other. The two parameters differed considerably among the patients, showing that the accumulation of contrast medium was higher in some tumors than in others. Tumor contrast enhancement increased with increasing PERF, suggesting that the accumulation of contrast medium in the tumors was determined mainly by the effective tissue perfusion. There was also a clear correlation between tumor contrast enhancement and TS. The tumors showing a high accumulation of contrast medium were more difficult to heat than those showing a low accumulation. CONCLUSION: The results indicate that contrast enhanced computed tomography images may give information about the treatment temperatures that can be achieved in clinical hyperthermia of breast carcinoma. The computed tomography images may possibly be used to predict those tumors that can be heated to therapeutic temperatures.

Body Temperature↗

31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma xenograft lines: tumour bioenergetic status and blood supply.

Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice were subjected to 31P-nuclear magnetic resonance (31P-NMR) spectroscopy in vivo. The following resonances were detected: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma, alpha and beta (NTP gamma, alpha and beta). The main purpose of the work was to search for possible relationships between 31P-NMR resonance ratios and tumour pH on the one hand and blood supply per viable tumour cell on the other. The latter parameter was measured by using the 86Rb uptake method. Tumour bioenergetic status [the (PCr + NTP beta)/Pi resonance ratio], tumour pH and blood supply per viable tumour cell decreased with increasing tumour volume for five of the six xenograft lines. The decrease in tumour bioenergetic status was due to a decrease in the (PCr + NTP beta)/total resonance ratio as well as an increase in the Pi/total resonance ratio. The decrease in the (PCr + NTP beta)/total resonance ratio was mainly a consequence of a decrease in the PCr/total resonance ratio for two lines and mainly a consequence of a decrease in the NTP beta/total resonance ratio for three lines. The magnitude of the decrease in the (PCr + NTP beta)/total resonance ratio and the magnitude of the decrease in tumour pH were correlated to the magnitude of the decrease in blood supply per viable tumour cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the magnitude of this decrease was larger 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 31P-NMR spectrum between the tumour lines were probably caused by differences in the intrinsic biochemical properties of the tumour cells rather than by the differences in blood supply per viable tumour cell. Biochemical properties of particular importance included rate of respiration, glycolytic capacity and tolerance to hypoxic stress. On the other hand, tumour bioenergetic status and tumour pH were correlated to blood supply per viable tumour cell within individual tumour lines. These observations suggest that 31P-NMR spectroscopy may be developed to be a clinically useful method for monitoring tumour blood supply and parameters related to 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 can probably not be derived from a single 31P-NMR spectrum since correlations across tumour lines were not detected; additional information is needed.

Analysis of Variance↗