Novel Approaches to Imaging Tumor Metabolism

Tee, Sui Seng; Keshari, Kayvan R.

doi:10.1097/ppo.0000000000000111

Cited by 25 publications

(23 citation statements)

References 102 publications

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“…Hyperpolarized magnetic resonance spectroscopy (HP-MRS) is unique in its ability to deliver information on enzyme kinetics. Hyperpolarization describes a number of techniques that are used to enhance the polarization of nuclear spins, with dissolution dynamic nuclear polarization (dDNP) being the mostly widely used to study in vivo metabolism [ 16 ]. dDNP is based on polarizing nuclear spins in a frozen sample, where microwave irradiation is used to transfer polarization from an organic free radical to an NMR-visible metabolite of interest.…”

Section: Introductionmentioning

confidence: 99%

PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose

et al. 2017

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Cancer metabolism has emerged as an increasingly attractive target for interfering with tumor growth. Small molecule activators of pyruvate kinase isozyme M2 (PKM2) suppress tumor formation but have an unknown effect on established tumors. We demonstrate that TEPP-46, a PKM2 activator, results in increased glucose consumption, providing the rationale for combining PKM2 activators with the toxic glucose analog, 2-deoxy-D-glucose (2-DG). Combination treatment resulted in reduced viability of a range of cell lines in standard cell culture conditions at concentrations of drugs that had no effect when used alone. This effect was replicated in vivo on established subcutaneous tumors. We further demonstrated the ability to detect acute metabolic differences in combination treatment using hyperpolarized magnetic resonance spectroscopy (MRS). Combination treated tumors displayed a higher pyruvate to lactate 13 C-label exchange 2 hr post-treatment. This ability to assess the effect of drugs non-invasively may accelerate the implementation and clinical translation of drugs that target cancer metabolism.

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Section: Introductionmentioning

confidence: 99%

PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose

et al. 2017

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“…They provide clinically valuable information that can guide therapeutic decisions [1][2][3] . Radioactive tracers, such as 18 fluorodeoxyglucose (FDG), in combination with CT take advantage of unique features of cancer cells such as their highly proliferative and glycolytic nature, allowing identification of small tumors that are not detectable by anatomical imaging alone 4 . Such detection can result in clinically meaningful outcomes for patients, as surgical or medical interventions can be undertaken at lower tumor burden, i.e.…”

Section: Introductionmentioning

confidence: 99%

In vivodeuterated water labeling allows tumor visualization via deuterium magnetic resonance spectroscopic imaging of cholesterol

Assmann

Brender

Farthing

et al. 2019

Preprint

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In vivo deuterated water ( 2 H2O) labeling leads to deuterium ( 2 H) incorporation into biomolecules of proliferating cells and provides the basis for its use in cell kinetics research. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with 2 H and, therefore, could be visualized by deuterium magnetic resonance imaging (dMRI) following a short in vivo 2 H2O labeling period. We initiated systemic 2 H2O labeling in an HT-29 xenograft model and performed dMRI following 7 and 14 days of in vivo tumor growth and labeling. We show that small tumors, not otherwise distinct from normal tissue by anatomical MRI, were readily apparent on dMRI following 7 days of labeling. This novel labeling-imaging approach allows safe and nonradioactive, in vivo detection of cancer. Our method could be well suited for clinical settings that require serial imaging where repeated exposure to radiotracers should be avoided.

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“…Advances in technology have accelerated the use of molecular probes to study tumor metabolism in the clinic. Radiotracer such as 18 F-labeled fludeoxyglucose ( 18 FDG) is widely used to investigate changes in tumor glycolysis, while 18 F-choline and 18 F-(2S,4R)4-fluoroglutamine ( 18 FGln) are commonly used to study lipid and glutamine/glutamate metabolism, respectively ( 12 , 13 ). Non-radioactive methods such as magnetic resonance imaging (MRI) allow the visualization of changes in tissue morphology, while magnetic resonance spectroscopy (MRS) reveals some aspects of tissue metabolism ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibiting Glycine Decarboxylase Suppresses Pyruvate-to-Lactate Metabolism in Lung Cancer Cells

et al. 2018

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Glycine decarboxylase (GLDC) gene is frequently upregulated in various types of cancer including lung, prostate and brain. It catabolizes glycine to yield 5,10-methylenetetrahydrofolate, an important substrate in one-carbon metabolism for nucleotide synthesis. In this study, we used exon splicing modulating steric hindrance antisense oligonucleotide (shAON) to suppress GLDC expression and investigated its effect on pyruvate metabolism via hyperpolarized carbon-13 magnetic resonance spectroscopy (MRS). The MRS technique allows us to study in vivo metabolic flux in tumor tissues with/without GLDC-shAON intervention. Here, we show that GLDC-shAON treatment is able to suppress lung cancer cell growth and tumorigenesis, both in vitro and in vivo. The carbon-13 MRS results indicated that the conversion of pyruvate into lactate in GLDC-shAON-treated tumor tissues was significantly reduced, when compared with the control groups. This observation corroborated with the reduced activity of lactate dehydrogenase and pyruvate dehydrogenase in GLDC-shAON-treated lung cancer cells and tumor tissues. Glycolysis stress test showed that extracellular acidification rate was significantly suppressed after GLDC-shAON treatment. Besides lung cancer, the antitumor effect of GLDC-shAON was also observed in brain, liver, cervical, and prostate cancer cell lines. Furthermore, it enhanced the treatment efficacy of cisplatin in lung cancer cells. Taken together, our findings illustrate that pyruvate metabolism decreases upon GLDC inhibition, thereby starving cancer cells from critical metabolic fuels.

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Novel Approaches to Imaging Tumor Metabolism

Cited by 25 publications

References 102 publications

PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose

PKM2 activation sensitizes cancer cells to growth inhibition by 2-deoxy-D-glucose

In vivodeuterated water labeling allows tumor visualization via deuterium magnetic resonance spectroscopic imaging of cholesterol

Inhibiting Glycine Decarboxylase Suppresses Pyruvate-to-Lactate Metabolism in Lung Cancer Cells

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