Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours

Walenta, Stefan; Dellian, Marc; Goetz, Alwin E.; Kuhnle, G. E. H.; Mueller‐Klieser, Wolfgang

doi:10.1038/bjc.1992.417

Cited by 20 publications

(11 citation statements)

References 11 publications

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“…An oxygenation status with median pO 2 values < 10 mmHg would therefore coincide with average blood flow values <0.48 ml/(g, rain) in this experimental tumor. This latter flow value is similar to that described by Walenta et al 33, who found a 'breakpoint' in the correlation between [ATP] and flow at roughly 0.4-0.5 ml/ (g. rain) for A-Mel 3 tumors in hamsters.…”

Section: Interpretation Of Datasupporting

confidence: 82%

Is there a critical tissue oxygen tension for bioenergetic status and cellular pH regulation in solid tumors?

Vaupel

1996

Experientia

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Bioenergetic and metabolic status have been correlated with tissue oxygenation in murine fibrosarcomas (FSaII) of varying sizes (44-600 mm3). Ratios of beta-nucleoside triphosphates to inorganic phosphate (beta NTP/P) and phosphocreatine to inorganic phosphate (PCr/P(i)) ratios derived from 31P nuclear magnetic resonance spectroscopy (NMR) were positively correlated to median tissue O2 tension (pO2) values using O2-sensitive needle electrodes. pH declined during growth with intracellular acidosis being evident in tumors > 350 mm3. Whereas lactic acid formation greatly contributed to this decline in small and medium-sized tumors, adenosine triphosphate (ATP) hydrolysis and slowing down of the activities of pumps involved in cellular pH regulation seem to be major factors responsible for intracellular acidification in bulky tumors. PCr levels decreased at an early growth stage, whilst ATP concentrations dropped in bulky malignancies only, coinciding with a decrease in adenylate energy charge and a substantial rise in the levels of total P(i). On average, median pO2 values of ca. 10 mmHg represent a critical threshold for energy metabolism. At higher median O2 tensions, levels of ATP, phosphomonoester (PME) and total P(i) were relatively constant. This coincided with intracellular alkalosis or neutrality and stable adenylate ratios. On average, median pO2 values < 10 mmHg coincided with intracellular acidosis, ATP depletion, a drop in energy charge and rising P(i) levels.

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Section: Interpretation Of Datasupporting

confidence: 82%

Is there a critical tissue oxygen tension for bioenergetic status and cellular pH regulation in solid tumors?

Vaupel

1996

Experientia

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“…Similar observations have been described for other experimental tumour systems. In an amelanotic hamster melanoma (A-Mel-3), ATP concentrations remained constant as long as blood flow values were above 0.4 ml g' min-' (Walenta et al, 1992). This finding is based on pixel-to-pixel correlations between microregional ATP concentrations and flow data.…”

Section: Resultsmentioning

confidence: 85%

“…The concentrations of the adenylate phosphates were then determined using reversed-phase high-performance liquid chromatography (HPLC) techniques at 254 nm (for more details see Kruger et al., 1991;Schaefer et al, 1993). Concentrations were expressed as j.mol per g tissue wet weight.Determination of microregional A TP distribution Before preparing the rapidly frozen tumours for HPLC analysis, approximately 30% of the tumour mass was separated, cut at -25°C in a cryostat into 5-nm sections and used for ATP bioluminescence measurements to assess the microregional ATP distribution using single-photon imaging and quantitative bioluminescence (for methodological details see Walenta et al, 1992;Schaefer et al, 1993). The spatial resolution gained by this method is about 50 jam, thus revealing information about the intra-tumour variability of the ATP levels in relation to histological details.…”

mentioning

confidence: 99%

Stable bioenergetic status despite substantial changes in blood flow and tissue oxygenation in a rat tumour

Vaupel

Kelleher²,

Engel³

1994

Br J Cancer

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al., 1985;Evelhoch et al., 1986;Tozer et al., 1987; Vaupel et al., 1989a, b;Steen & Graham, 1991 (Bremner et al., 1993). The reduction in the oxygenation status caused by hydralazine is insufficient for detection by 31P-NMR in human xenografted tumours, whereas in RIF-1, SCCVII/Ha and KHT murine tumours large increases in the Pi/total phosphate ratio are found (Bremner et al., 1991;Adams et al., 1992). In the light of these discrepancies, a number of relevant issues need to be clarified regarding the relationship between energy status and tumour blood flow. In the present study, the key questions were as follows:(1) Do nected to a ratemeter (FHT 1100 FAG Kugelfischer, Erlangen, Germany). The method of evaluation of TBF was identical to that described earlier (Kluge et al., 1992). Measurements were performed on tumours of varying sizes at 20 min intervals before application of TNF-x and at 30 min intervals thereafter over a total time period of 2 h post treatment. In all experiments performed in this study, animals were allowed to stabilise following the surgical procedures. Measurements commenced once constant baseline readings for MABP and flow were obtained for at least 20 min.Laser Dopplerflowmetry A Periflux model PF 3 dual-channel laser Doppler flowmeter was used for this study (2 mW He-Ne laser, wavelength 632.8 nm; Perimed, Stockholm, Sweden , 1989a, 1991). Measurements were made either on tumours of varying sizes or before and 120 min after acute flow changes upon TNF-a application.Measurement ofglobal concentrations of adenylate phosphates in perchloric acid extracts In order to obtain mean (global) levels of adenylate phosphates, the tumour-bearing hindfoot was rapidly frozen and the tumours (n = 12) were prepared under liquid nitrogen and stored at -80°C for further processing. In a first series of experiments, tumours of varying sizes were analysed. In another series, tumours were assayed before or 120 min after administration of TNF-o. Each deep-frozen tumour was ground to a fine powder and freeze dried. For determination of ATP, ADP and AMP levels, aliquots of freeze-dried tissue were extracted with 0.66 M perchloric acid, centrifuged and the supernatant neutralised with 2 M potassium hydroxide. The concentrations of the adenylate phosphates were then determined using reversed-phase high-performance liquid chromatography (HPLC) techniques at 254 nm (for more details see Kruger et al., 1991;Schaefer et al., 1993). Concentrations were expressed as j.mol per g tissue wet weight.Determination of microregional A TP distribution Before preparing the rapidly frozen tumours for HPLC analysis, approximately 30% of the tumour mass was separated, cut at -25°C in a cryostat into 5-nm sections and used for ATP bioluminescence measurements to assess the microregional ATP distribution using single-photon imaging and quantitative bioluminescence (for methodological details see Walenta et al., 1992;Schaefer et al., 1993). The spatial resolution gained by this method is about 50 jam, thus revealing informatio...

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“…The BLI clearly indicates high concentrations of ATP in viable cell regions of the periphery. Furthermore, the studies show that high levels of glucose are found in the tumor periphery while necrotic tumor centers exhibited high lactate levels (Walenta, Dellian et al 1992). The metabolic switch to aerobic glycolysis and enhanced lactate production is characteristic for aggressive tumor cells and a factor for tumor response and treatment outcome.…”

Section: Use Of Bli In Oncology Researchmentioning

confidence: 99%

Bioluminescence Applications in Preclinical Oncology Research

Kalra¹,

Bally²

2012

Bioluminescence - Recent Advances in Oceanic Measurements and Laboratory Applications

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Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours

Cited by 20 publications

References 11 publications

Is there a critical tissue oxygen tension for bioenergetic status and cellular pH regulation in solid tumors?

Is there a critical tissue oxygen tension for bioenergetic status and cellular pH regulation in solid tumors?

Stable bioenergetic status despite substantial changes in blood flow and tissue oxygenation in a rat tumour

Bioluminescence Applications in Preclinical Oncology Research

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