Two-compartment model for determination of glycolytic rates of solid tumors byin vivo13C NMR spectroscopy

Artemov, Dmitri; Bhujwalla, Zaver M.; Pilatus, Ulrich; Glickson, Jerry D.

doi:10.1002/(sici)1099-1492(199812)11:8<395::aid-nbm536>3.0.co;2-r

Cited by 32 publications

(35 citation statements)

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“…Analysis of the images yielded a measure of the entire volume of each tumor and estimation of the percent necrosis, as pre-viously described (13). The volume of the tumors ranged from 0.35 to 1.5 cm 3 , with a mean of 0.84 Ϯ 0.1 cm 3 . Percent necrosis ranged from 1 to 5%, demonstrating the predominance of viable tissue in all of the tumors.…”

Section: Resultsmentioning

confidence: 99%

“…Detailed kinetic MRS studies of 13 C-labeled glucose consumption and lactate synthesis were previously performed in cultured breast cancer cells (12,20,21,24). Similar in vivo MRS studies of tumors in animal models focused on evaluating lactate clearance (30) or lactate synthesis and clearance (3,22). Here, we describe a novel dynamic in vivo 13 C MRS study of both glucose metabolism and lactate synthesis in orthotopic MCF7 human breast tumors.…”

Section: Magnetic Resonance Spectroscopy (Mrs) With Use Of Enriched [mentioning

confidence: 99%

“…Here, we describe a novel dynamic in vivo 13 C MRS study of both glucose metabolism and lactate synthesis in orthotopic MCF7 human breast tumors. The time courses of both [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose and [3-13 C]lactate were simultaneously measured and further analyzed by a physiological model, yielding the tumor kinetic parameters of glycolysis, glucose perfusion and lactate clearance. Furthermore, changes in these parameters served to assess the response of the tumors to tamoxifen, the leading antiestrogenic drug in breast cancer management.…”

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confidence: 99%

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Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo ¹³C MRS

Rivenzon-Segal

Margalit

Degani

2002

American Journal of Physiology-Endocrinology and Metabolism

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Rivenzon-Segal, Dalia, Raanan Margalit, and Hadassa Degani. Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo 13 C MRS. Am J Physiol Endocrinol Metab 283: E623-E630, 2002. First published May 21, 2002 10.1152/ajpendo.00050.2002.-Enhanced glycolysis represents a striking feature of cancers and can therefore serve to indicate a malignant transformation. We have developed a noninvasive, quantitative method to characterize tumor glycolysis by monitoring 13 C-labeled glucose and lactate with magnetic resonance spectroscopy. This method was applied in MCF7 human breast cancer implanted in the mammary gland of female CD1-NU mice and was further employed to assess tumor response to hormonal manipulation with the antiestrogen tamoxifen. Analysis of the kinetic data based on a unique physiological-metabolic model yielded the rate parameters of glycolysis, glucose perfusion, and lactate clearance in the tumor, as well as glucose pharmacokinetics in the plasma. Treatment with tamoxifen induced a twofold reduction in the rate of glycolysis and of lactate clearance but did not affect the other parameters. This metabolic monitoring can thus serve to evaluate the efficacy of new selective estrogen receptor modulators and may be further extended to improve diagnosis and prognosis of breast cancer. magnetic resonance spectroscopy; [ 13 C]glucose; [ 13 C]lactate GLUCOSE, AN ESSENTIAL COMPOUND for many living organisms, is an important carbon source for energy-producing metabolic processes and for the synthesis of low molecular weight and macromolecular products. For more than 70 years, it has been known that cancer cells utilize and metabolize glucose at high rates, even in the presence of high oxygen concentrations, to form mainly lactate (36). Indeed, lactate was found to be present in tumors at levels much higher than in the corresponding normal tissues (9,15,16,25). Furthermore, quantitative studies of biopsies from human cancers have indicated a positive correlation between tumor lactate concentration and incidence of metastasis (5,26,34,35). Increased glycolysis is associated with higher glucose uptake and metabolism, and it is now utilized as an indicator of malignancy by applying positron emission tomography (PET) with the glucose analog 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) (2,23,29,33). FDG-PET has also been used for prognostic evaluation, for monitoring tumor therapy, and for early detection of recurrent cancer growth (2, 29, 33). C magnetic resonance spectroscopy (MRS) with use of enriched [13 C]glucose can also serve to monitor in vivo glucose metabolism. Specifically, it monitors glucose uptake and consumption, and it traces other metabolites into which the 13 C label is incorporated, including lactate (28). Detailed kinetic MRS studies of 13 C-labeled glucose consumption and lactate synthesis were previously performed in cultured breast cancer cells (12,20,21,24). Similar in vivo MRS studies of tumors in animal models focused on evaluating lactate clearance (30) or lactate synthesi...

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Section: Resultsmentioning

confidence: 99%

Section: Magnetic Resonance Spectroscopy (Mrs) With Use Of Enriched [mentioning

confidence: 99%

mentioning

confidence: 99%

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Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo ¹³C MRS

Rivenzon-Segal

Margalit

Degani

2002

American Journal of Physiology-Endocrinology and Metabolism

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“…As shown in Fig. 5, 13 C-labeled glucose can be used to determine the glycolytic rate of a tumor [95], [96] and 13 C-labeled choline can be used to follow choline membrane metabolism [97]. 13 C-labeled precursors have been used in high resolution 13 C MR studies of cells or tissue extracts, in noninvasive cell perfusion studies of isolated cells, and in infusion studies of animal tumor models.…”

Section: B 13 C Mrsmentioning

confidence: 99%

“…In poorly differentiated transplanted tumors, [1 −13 C]-labeled glucose is metabolized to lactate [95], [99]- [101], whereas well-differentiated tumors such as rat hepatoma demonstrated metabolic behavior close to the tissue of origin [102]. Lactate levels in tumors are related to several parameters such as glycolytic rates, blood flow, glucose supply, hypoxia, venous clearance, extent of necrosis, and degree of inflammatory cell infiltration [103].…”

Section: B 13 C Mrsmentioning

confidence: 99%

Molecular Imaging of Cancer: Applications of Magnetic Resonance Methods

et al. 2005

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Cancer is a complex disease exhibiting a host of phenotypic diversities. Noninvasive multinuclear magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) provide an array of capabilities to characterize and understand several of the vascular, metabolic, and physiological characteristics unique to cancer. The availability of targeted contrast agents has widened the scope of MR techniques to include the detection of receptor and gene expression. In this paper, we have highlighted the application of several MR techniques in imaging and understanding cancer.

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Metabolism of alternative substrates and the bioenergetic status of EMT6 tumor cell spheroids

Wehrle

McGovern

et al. 2000

NMR Biomed.

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Two-compartment model for determination of glycolytic rates of solid tumors byin vivo13C NMR spectroscopy

Cited by 32 publications

References 31 publications

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo ¹³C MRS

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo ¹³C MRS

Molecular Imaging of Cancer: Applications of Magnetic Resonance Methods

Metabolism of alternative substrates and the bioenergetic status of EMT6 tumor cell spheroids

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Two-compartment model for determination of glycolytic rates of solid tumors byin vivo13C NMR spectroscopy

Cited by 32 publications

References 31 publications

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo 13C MRS

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo 13C MRS

Molecular Imaging of Cancer: Applications of Magnetic Resonance Methods

Metabolism of alternative substrates and the bioenergetic status of EMT6 tumor cell spheroids

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Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo ¹³C MRS

Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo ¹³C MRS