Abnormal liver metabolism in cancer patients detected by31P MR spectroscopy

Abstract

There is accumulating evidence indicating that the presence of malignant disease is accompanied by profound changes of liver metabolism in the cancer‐bearing host. We previously reported [P. C. Dagnelie, J. D. Bell, ­S. C. R. Williams, T. E. Bates, P. D. Abel and C. S. Foster, Br. J. Cancer 67, 1303–1309 (1993)] marked 31P MRS‐detected alterations in phosphorylation status as well as in phospholipid and glucose metabolism in the liver of rats bearing Dunning prostate tumours. The aim of the present study was first to define abnormalities in liver metabolism in patients with a distant malignancy using 31P MRS, and second to explore the value of including long‐TR sequences in clinical 31P MRS studies of the liver. Liver metabolite levels were expressed relative to total MR‐detectable phosphate. In weight‐losing (WL, n = 10), but not in weight‐stable (WS, n = 13) cancer patients, liver phosphomonoester (PME) levels were significantly elevated, whereas phosphodiester (PDE) levels were reduced when compared with age‐matched healthy subjects (n = 12). The TR 20:1 s ratio of PDE was increased in WS and WL cancer patients, suggesting longer T1. At TR 20 s, but not at TR 1 s, ATP levels were significantly reduced in in WS and WL cancer patients compared with healthy subjects; similarly, Pi levels were reduced in WL patients at TR 20 and 5s, but not at TR 1 s. ATP:Pi ratios were unchanged regardless of TR. pH values increased in the order: healthy < cancer‐WS < cancer‐WL. The PME chemical shift had significantly moved downfield in cancer patients, reflecting increased contributions from glycolytic/gluconeogenic intermediates. The observed changes in PME are consistent with previous reports suggesting increased gluconeogenesis in the liver of patients with a distant malignant tumour. Furthermore, our data support the use of including long‐TR sequences in clinical 31P MRS liver studies. Copyright © 1999 John Wiley & Sons, Ltd.

Hepatic sugar phosphate levels reflect gluconeogenesis in lung cancer: simultaneous turnover measurements and 31P magnetic resonance spectroscopy in vivo

“…Five spectra were collected with a 640 µs Hanning-sinc shaped radio frequency pulse, resulting in a flip angle of 135 m in the centre of the coil and 60 m (weighted average) in the liver volume with a repetition time of 1 s (40 acquisitions). We demonstrated previously [17] that use of repetition times of 1 s and 20 s gives similar differences for PME levels between WL\ weight-stable cancer patients and healthy control subjects. Furthermore, saturation at the repetition time of 1 s and the pulse angle of 60 m used in our study is maximally 15 % for PME (relative to β-ATP) and 30 % for PDE (relative to β-ATP) [26].…”

“…Quantification of spectral peak areas was performed using the Numaris-3 software package (Siemens AG), including polynomial baseline correction followed by frequency domain curve fitting [27]. Metabolite concentrations were calculated from peak areas and expressed relative to total MR-detectable phosphate, as described previously [17]. In each experiment the average of five subsequent $"P MR spectra was used for calculations.…”

“…In a previous $"P MR spectroscopy (MRS) study, markedly elevated levels of phosphomonoesters (PME) and reduced levels of phosphodiesters (PDE) were observed in the tumour-free (i.e. non-metastatic) livers of weight-losing (WL) cancer patients with various tumour types [17].…”

Quantitative proton magnetic resonance spectroscopy of the normal liver and malignant hepatic lesions at 3.0 Tesla

“…According to Dagnelie et al [14] there is accumulating evidence indicating that the presence of malignant disease is accompanied by profound changes of liver metabolism. Therefore, the data for normal-appearing liver parenchyma of patients and for liver parenchyma of volunteers were considered separately, in addition.…”

Influence of preculture on the prefreeze and postthaw characteristics of hepatocytes

“…5). Significant levels of 6PG have not been measured in extracts from homogenized fresh liver (Changani et al, 1996(Changani et al, , 1999Dagnelie et al, 1999;Harvey et al, 1999). The pentose phosphate pathway generates reducing power (in the form of NADPH) for the reduction of oxidized glutathione and is necessary for the prevention and repair of cellular oxidative damage (Voet and Voet, 1995).…”