Magnetic Resonance Spectroscopy for Detection of 2-Hydroxyglutarate as a Biomarker for IDH Mutation in Gliomas

Leather, Thomas; Jenkinson, Michael D.; Das, Kumar; Poptani, Harish

doi:10.3390/metabo7020029

Cited by 51 publications

(39 citation statements)

References 66 publications

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“…MRS uses the proton signals to determine relative concentrations of target metabolites rather than an anatomical image. In various studies, MRS has been shown capable of identifying regions of tissue enriched with stem-like cell-enriched foci [131], detecting tumours with mutations in the isocitrate dehydrogenase (IDH) genes [132,133], and assessing response to various therapies such as radiation and PI3K/mTOR inhibitors [134,135]. Further, the use of hyperpolarized (HP) contrast agents can significantly increase the sensitivity of MRS by enhancing the signal-to-noise ratio [136,137].…”

Section: Medical Imaging and Histopathologymentioning

confidence: 99%

The biology and mathematical modelling of glioma invasion: a review

Alfonso

Talkenberger

Seifert

et al. 2017

J. R. Soc. Interface.

183

163

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Adult gliomas are aggressive brain tumours associated with low patient survival rates and limited life expectancy. The most important hallmark of this type of tumour is its invasive behaviour, characterized by a markedly phenotypic plasticity, infiltrative tumour morphologies and the ability of malignant progression from low-to high-grade tumour types. Indeed, the widespread infiltration of healthy brain tissue by glioma cells is largely responsible for poor prognosis and the difficulty of finding curative therapies. Meanwhile, mathematical models have been established to analyse potential mechanisms of glioma invasion. In this review, we start with a brief introduction to current biological knowledge about glioma invasion, and then critically review and highlight future challenges for mathematical models of glioma invasion.

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Section: Medical Imaging and Histopathologymentioning

confidence: 99%

The biology and mathematical modelling of glioma invasion: a review

Alfonso

Talkenberger

Seifert

et al. 2017

J. R. Soc. Interface.

183

163

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“…In hypoxic environments where glucose metabolism is diverted to anaerobic lactate production, mutations in mitochondrial IDH2 provide a continued source of citrate for lipid synthesis, by allowing reductive carboxylation of glutamine‐derived α‐KG . The oncometabolite 2‐hydroxyglutarate is produced by many cancer‐specific IDH1 and IDH2 mutations, and has widespread epigenetic effectors by altering DNA methylation …”

Section: Tumor Progression and Regressionmentioning

confidence: 99%

“…The picture is further complicated because ChoK is not the only enzyme that contributes to PC accumulation; it can be produced directly by the actions of PLC on PtdCho, or by the hydrolysis of GPC as a source of additional choline for subsequent phosphorylation. Recent MRS applications have been used to detect changes in choline metabolism due to IDH mutations in glioma, explore the role of the glycerophosphodiesterase genes GDPD5 and GDPD6 on breast cancer cell migration/invasion, and profile metabolic changes in response to HIF1 and HIF2 suppression …”

Section: Imaging Metabolic Lipid Changesmentioning

confidence: 99%

Imaging of cancer lipid metabolism in response to therapy

et al. 2019

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Lipids represent a diverse array of molecules essential to the cell's structure, defense, energy, and communication. Lipid metabolism can often become dysregulated during tumor development. During cancer therapy, targeted inhibition of cell proliferation can likewise cause widespread and drastic changes in lipid composition. Molecular imaging techniques have been developed to monitor altered lipid profiles as a biomarker for cancer diagnosis and treatment response. For decades, MRS has been the dominant non-invasive technique for studying lipid metabolite levels. Recent insights into the oncogenic transformations driving changes in lipid metabolism haverevealed new mechanisms and signaling molecules that can be exploited using optical imaging, mass spectrometry imaging, and positron emission tomography. These novel imaging modalities have provided researchers with a diverse toolbox to examine changes in lipids in response to a wide array of anticancer strategies including chemotherapy, radiation therapy, signal transduction inhibitors, gene therapy, immunotherapy, or a combination of these strategies. The understanding of lipid metabolism in response to cancer therapy continues to evolve as each therapeutic method emerges, and this review seeks to summarize the current field and areas of unmet needs.

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“…Despite the pervading observations that the IDH mutation not only causes an increase in 2HG but also a change in several other metabolites, either at the initial diagnosis (Figure ) or during assessment of response to treatment (Figure ), the change in the metabolomic pattern seems not to be regarded with much interest in the literature. This seems surprising because 2HG is a non‐invasive diagnosis and prognosis biomarker for IDH mutation, and it is druggable . Perhaps small cohort sizes collected by each individual study and the difficulty of integrating these data with other studies using different acquisition and processing parameters may provide an explanation for this low uptake by clinical centres.…”

Section: Mrs(i)‐detectable Metabolic Hallmarks Of Cancer: Applicationmentioning

confidence: 99%

Cancer metabolism in a snapshot: MRS(I)

2019

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The contribution of MRS(I) to the in vivo evaluation of cancer-metabolism-derived metrics, mostly since 2016, is reviewed here. Increased carbon consumption by tumour cells, which are highly glycolytic, is now being sampled by 13 C magnetic resonance spectroscopic imaging (MRSI) following the injection of hyperpolarized [1-13 C] pyruvate (Pyr). Hot-spots of, mostly, increased lactate dehydrogenase activity or flow between Pyr and lactate (Lac) have been seen with cancer progression in prostate (preclinical and in humans), brain and pancreas (both preclinical) tumours. Therapy response is usually signalled by decreased Lac/Pyr 13 C-labelled ratio with respect to untreated or nonresponding tumour. For therapeutic agents inducing tumour hypoxia, the 13 C-labelled Lac/bicarbonate ratio may be a better metric than the Lac/Pyr ratio. 31 P MRSI may sample intracellular pH changes from brain tumours (acidification upon antiangiogenic treatment, basification at fast proliferation and relapse). The steady state tumour metabolome pattern is still in use for cancer evaluation. Metrics used for this range from quantification of single oncometabolites (such as 2-hydroxyglutarate in mutant IDH1 glial brain tumours) to selected metabolite ratios (such as total choline to N-acetylaspartate (plain ratio or CNI index)) or the whole 1 H MRSI(I) pattern through pattern recognition analysis. These approaches have been applied to address different questions such as tumour subtype definition, following/predicting the response to therapy or defining better resection or radiosurgery limits. KEYWORDSanimal model study, cancer, cellular and molecular cancer imaging, hyperpolarized C-13, MRS and MRSI methods, phosphorus MRS/MRSI | TEMPORAL AND THEMATIC BOUNDARIES OF THE TOPICS COVEREDThe authors of this review declare at the outset that there is no intention of being exhaustive or systematic. The temporal boundaries reviewed will be modest: only relevant literature since 2016, chosen according to our bias. Earlier work or reviews will only be referred to in order to put recent findings in due perspective. Authors hope that this summary will give readers a picture of how far cancer metabolism analysis with MRS(I) has advanced and, perhaps, why it is not advancing further.For quite a long time MRS, rather than MRI, has been the only approach able to evaluate cancer metabolism. Nevertheless, the MRI-derived information related to cancer metabolism should not be forgotten: consider for example the chemical exchange saturation transfer (CEST) effect caused by exchangeable protons in water-derived images of glucose uptake and metabolism in tumours. 1,2 However, apart from these CESTrelated studies, we should acknowledge that most information about cancer metabolism using MR still refers to MRS(I) acquisitions, which are the ones dealt with in our text.Supplementary Figure 1 shows a PUBMED search illustrating the different proportions of articles investigating several cancer types through MRS(I) approaches. The retrieved information can help unders...

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Magnetic Resonance Spectroscopy for Detection of 2-Hydroxyglutarate as a Biomarker for IDH Mutation in Gliomas

Cited by 51 publications

References 66 publications

The biology and mathematical modelling of glioma invasion: a review

The biology and mathematical modelling of glioma invasion: a review

Imaging of cancer lipid metabolism in response to therapy

Cancer metabolism in a snapshot: MRS(I)

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