Biochemical Investigation of Human Tumours in Vivo With Phosphorus-31 Magnetic Resonance Spectroscopy

Oberhaensli, Rolf D.; Bore, Peter J.; Rampling, RoyP.; Hilton‐Jones, David; Hands, L; Radda, G. K.

doi:10.1016/s0140-6736(86)92558-4

Cited by 180 publications

(71 citation statements)

References 13 publications

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“…Large monoester signals have been detected in MR spectra of a number of tumours in man, both hepatic and extrahepatic. These include secondary adenocarcinoma of the liver, Hodgkin's lymphoma, hepatoblastomas (Oberhaensli et al, 1986), neuroblastoma (Maris et al, 1985) and carcinoid metastases (Cox et al, 1988). The biochemical basis of these changes is, however, unclear.…”

Section: Discussionmentioning

confidence: 99%

“…31P magnetic resonance (MR) spectroscopic studies of human cancers have demonstrated a variety of biochemical abnormalities in malignant tissues, including pH shifts and raised phosphomonoesters (Oberhaensli et al, 1986;Cox et al, 1988;Ng et al, 1989;Glazer et al, 1989). MR spectroscopy therefore appears to offer a means of distinguishing between normal and neoplastic tissue, and of monitoring cellular energetics and biochemistry in response to treatment (Maris et al, 1985;Glaholm et al, 1989;Ng et al, 1987).…”

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confidence: 99%

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Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy

Dixon

Angus²,

Rajagopalan³

et al. 1991

Br J Cancer

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Summary Hepatic infiltration by lymphoma can be difficult to detect by conventional methods. We have studied 22 patients in vivo 31P magnetic resonance spectroscopy of the liver and compared the results with the clinical staging and assessment of liver involvement by computed tomography (CT), ultrasound (US), and liver function tests (LFTs). We find that the phosphomonoester (PME) to ATP, and the PME to Pi ratios are the best indication of liver involvement as in all the patients with liver involvement apparent on CT or US, these ratios were elevated (> 2 s.d. above the control mean). Of the patients with deranged LFTs but normal CT or US, five out of nine showed increased PME/ATP and PME/Pi ratios, and in the patients with normal LFTs and normal CT or US, three out of eight patients had raised PME ratios. Extracts of lymphomatous lymph nodes contain high concentrations of phosphoethanolamine which suggests that this compound is responsible for the increase in the PME peak. Eleven patients were studied again after chemotherapy, and those with initially raised PME/ATP and PME/Pi ratios all showed a decrease in these ratios towards normal. The

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy

Dixon

Angus²,

Rajagopalan³

et al. 1991

Br J Cancer

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“…The PME peak was mainly composed of phosphoethanolamine (PE), a precursor in phospholipid synthesis. Human studies of neuroblastoma and other tumours in vivo have also found a raised PME peak (Maris et al, 1985) and alkaline pHi relative to normal tissue in some brain tumours (Oberhaensli et al, 1986).The aim of this study was to investigate the phosphorus metabolism of normal brain and primary brain tumours and relate biochemical differences to histological features seen in the tumour biopsies taken within 24h of the MRS study. The phase modulated rotating frame imaging (PMRFI) technique was used (Blackledge et al, 1987) in which a double surface coil, placed over the region of interest, receives signal from a defined cylinder of tissue 6 cm in diameter to a depth of 6cm.…”

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confidence: 93%

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confidence: 99%

Human primary brain tumour metabolism in vivo: a phosphorus magnetic resonance spectroscopy study

Cadoux-Hudson

Blackledge²,

Rajagopalan³

et al. 1989

Br J Cancer

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Summary Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n=7) intracellular pH (pHi) of the brain was 7.03+0.02 (mean±s.e.m.). The pHi did not vary between superficial (2cm, majority grey matter) and deep brain (5cm, majority white matter). The relative concentrations of phosphocreatine (PCr) and phosphomonoesters (PME) to ATP were also constant with depth. The relative concentration of phosphodiesters (PDE) increased from superficial to deep in normal brain. The astrocytomas (n = 7, grade II-IV) were significantly more alkaline (pHi = 7.08 + 0.03), and contained more PCr and PME, with respect to ATP, than normal brain at similar depth. The meningiomas (n = 4) were also more alkaline (pHi = 7.19 + 0.02) with a raised PME level but reduced PCr. The reduction in meningioma PCr may be due to the significant necrosis (>20 %) seen in the surgical biopsies. No significant necrosis was seen in the gliomas. Previous in vitro studies suggest that increased PME may be due to accumulation of phosphoethanolamine (PE), a phospholipid precursor. These results suggest that human primary brain tumours characteristically are more alkaline with increased PME than normal brain.Magnetic resonance spectroscopy (MRS) offers a noninvasive, non-disruptive method of studying intra-cellular metabolism in vivo. The development of wide bore magnets has allowed 31P MRS to be applied to the study of tumours in humans. Differences between the biochemistry of normal and neoplastic tissues have been used to design optimum forms of chemotherapy. This technique gives information on phosphocreatine (PCr), ATP, inorganic phosphate (Pi) levels and phosphomonester (PME) and phosphodiester (PDE) containing compounds within the cell, and on intracellular pH (pHi) (Radda, 1986).PCr, ATP and Pi are compounds involved in energy transfer within the cell. The intracellular levels of these compounds are determined in part by the balance between substrate supply and energy demand. PME and PDE peaks contain signal derived from compounds which are involved in phospholipid synthesis and degradation . Relative levels of PME and PDE may reflect differing rates of cell turnover. Animal and tissue culture tumour models have been studied using phosphorus MRS (Daly et al., 1987;Miceli et al., 1988). These studies have shown a consistently raised PME peak within the neoplastic cell. The PME peak was mainly composed of phosphoethanolamine (PE), a precursor in phospholipid synthesis. Human studies of neuroblastoma and other tumours in vivo have also found a raised PME peak (Maris et al., 1985) and alkaline pHi relative to normal tissue in some brain tumours (Oberhaensli et al., 1986).The aim of this study was to investigate the phosphorus metabolism of normal brain and primary brain tumours and relate biochemical differences to histological features seen in the tumour biopsies taken within 24h of the MRS study. The phase modulated r...

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“…Tumours have been investigated by phosphorus NMR in experimental [2,3] and clinical [4] situations. Metabolic response to therapy [2,5] has been studied and a correlation between blood flow and tumour energy status has been reported [6].…”

Section: Introductionmentioning

confidence: 99%

Induction of tumour hypoxia by a vasoactive agent A combined NMR and radiobiological study

Dunn¹,

Frostick²,

Adams³

et al. 1989

FEBS Letters

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The effect of hydralazine treatment on 3 murine tumours (RIF-I, KHT and 16/C) was monitored using 31P-NMR. Changes in the 31p-NMR spectrum are compared with measurements of radiobiological hypoxic fraction (RHF) in the RIF-1 and KHT. Hydralazine is known to reduce temporarily blood flow in experimental tumours, and thus cause a transient increase in the RHF to 100% (in RIF-1 and KHT). This correlates with a decline in energy status as measured by 31p-NMR (i.e. there was an increase in Pi in all three tumours). Time-course data from the RIF-I and KHT tumours show that maintenance of anaesthesia prolongs the hypoxia induced by hydralazine.

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Biochemical Investigation of Human Tumours in Vivo With Phosphorus-31 Magnetic Resonance Spectroscopy

Cited by 180 publications

References 13 publications

Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy

Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy

Human primary brain tumour metabolism in vivo: a phosphorus magnetic resonance spectroscopy study

Induction of tumour hypoxia by a vasoactive agent A combined NMR and radiobiological study

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