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NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS

BACKGROUND: The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic reson...

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Autores principales: Kim, Lauren, De Feyter, Henk, de Graaf, Robin, Fulbright, Robert, Liu, Yanning, Rothman, Douglas, Baehring, Joachim, Blondin, Nicholas, Kim, Peter, Antonio, Omuro, Chiang, Veronica, Moliterno, Jennifer, Omay, Sacit Bulent, Piepmeier, Joseph, Corbin, Zachary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402410/
http://dx.doi.org/10.1093/noajnl/vdad070.060
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author Kim, Lauren
De Feyter, Henk
de Graaf, Robin
Fulbright, Robert
Liu, Yanning
Rothman, Douglas
Baehring, Joachim
Blondin, Nicholas
Kim, Peter
Antonio, Omuro
Chiang, Veronica
Moliterno, Jennifer
Omay, Sacit Bulent
Piepmeier, Joseph
Corbin, Zachary
author_facet Kim, Lauren
De Feyter, Henk
de Graaf, Robin
Fulbright, Robert
Liu, Yanning
Rothman, Douglas
Baehring, Joachim
Blondin, Nicholas
Kim, Peter
Antonio, Omuro
Chiang, Veronica
Moliterno, Jennifer
Omay, Sacit Bulent
Piepmeier, Joseph
Corbin, Zachary
author_sort Kim, Lauren
collection PubMed
description BACKGROUND: The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic resonance (MR) spectroscopic imaging technique coined Deuterium Metabolic Imaging (DMI) to measure the WE in multiple brain tumor types. METHODS: Twenty-one patients underwent DMI, acquired on a Bruker 4T MR scanner after oral administration of 0.75g/kg of deuterated glucose. The WE was defined as the ratio of deuterated lactate, representing glycolysis, over deuterated glutamate and glutamine, representing oxidative phosphorylation. We devised an interval scale from 0 to 2 for the WE RESULTS: The Wilcoxon rank sum test was performed to detect differences between groups. RESULTS: The WE measurements for the largest groups, by diagnosis, showed: glioblastoma (n=9, mean=1.67); astrocytoma, IDH-mutant, WHO grade 3 (n=2, mean=0.25); oligodendroglioma, WHO grade 3 (n=3, mean=0.5); low grade glioma, IDH-mutant (n=2, mean=0); and meningioma, WHO grade 2 (n=2, mean=0). The WE for high-grade tumors (n=15, mean=1.27) was significantly different from the WE for low-grade tumors (n=5, mean=0), with a p=0.010. The WE for IDH wild type gliomas (n=9, mean=1.67) was significantly different from the WE for IDH-mutant gliomas (n=9, mean=0.44), with a p=0.007. Analysis is ongoing. CONCLUSIONS: DMI successfully and non-invasively detects the WE in many types of brain tumors. The WE was larger in high-grade tumors as compared to low-grade tumors, and the WE was larger in IDH wild type gliomas as compared to IDH-mutant gliomas. If validated with future studies, our results suggest that DMI is a useful tool to measure differences in the metabolism of brain tumors with different clinical behaviors.
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spelling pubmed-104024102023-08-05 NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS Kim, Lauren De Feyter, Henk de Graaf, Robin Fulbright, Robert Liu, Yanning Rothman, Douglas Baehring, Joachim Blondin, Nicholas Kim, Peter Antonio, Omuro Chiang, Veronica Moliterno, Jennifer Omay, Sacit Bulent Piepmeier, Joseph Corbin, Zachary Neurooncol Adv Final Category: Neuroimaging BACKGROUND: The Warburg Effect (WE) is a metabolic change in which tumors favor glycolysis over oxidative phosphorylation and has been linked to cancer aggressiveness. Mutations in the isocitrate dehydrogenase (IDH) genes in gliomas are associated with improved outcomes. We deployed a magnetic resonance (MR) spectroscopic imaging technique coined Deuterium Metabolic Imaging (DMI) to measure the WE in multiple brain tumor types. METHODS: Twenty-one patients underwent DMI, acquired on a Bruker 4T MR scanner after oral administration of 0.75g/kg of deuterated glucose. The WE was defined as the ratio of deuterated lactate, representing glycolysis, over deuterated glutamate and glutamine, representing oxidative phosphorylation. We devised an interval scale from 0 to 2 for the WE RESULTS: The Wilcoxon rank sum test was performed to detect differences between groups. RESULTS: The WE measurements for the largest groups, by diagnosis, showed: glioblastoma (n=9, mean=1.67); astrocytoma, IDH-mutant, WHO grade 3 (n=2, mean=0.25); oligodendroglioma, WHO grade 3 (n=3, mean=0.5); low grade glioma, IDH-mutant (n=2, mean=0); and meningioma, WHO grade 2 (n=2, mean=0). The WE for high-grade tumors (n=15, mean=1.27) was significantly different from the WE for low-grade tumors (n=5, mean=0), with a p=0.010. The WE for IDH wild type gliomas (n=9, mean=1.67) was significantly different from the WE for IDH-mutant gliomas (n=9, mean=0.44), with a p=0.007. Analysis is ongoing. CONCLUSIONS: DMI successfully and non-invasively detects the WE in many types of brain tumors. The WE was larger in high-grade tumors as compared to low-grade tumors, and the WE was larger in IDH wild type gliomas as compared to IDH-mutant gliomas. If validated with future studies, our results suggest that DMI is a useful tool to measure differences in the metabolism of brain tumors with different clinical behaviors. Oxford University Press 2023-08-04 /pmc/articles/PMC10402410/ http://dx.doi.org/10.1093/noajnl/vdad070.060 Text en © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Neuroimaging
Kim, Lauren
De Feyter, Henk
de Graaf, Robin
Fulbright, Robert
Liu, Yanning
Rothman, Douglas
Baehring, Joachim
Blondin, Nicholas
Kim, Peter
Antonio, Omuro
Chiang, Veronica
Moliterno, Jennifer
Omay, Sacit Bulent
Piepmeier, Joseph
Corbin, Zachary
NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
title NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
title_full NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
title_fullStr NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
title_full_unstemmed NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
title_short NEIM-11 DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS
title_sort neim-11 deuterium metabolic imaging (dmi) detects a larger warburg effect in high-grade brain tumors and in idh wild type gliomas
topic Final Category: Neuroimaging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402410/
http://dx.doi.org/10.1093/noajnl/vdad070.060
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