Cargando…

BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO

The Warburg effect, characterized by elevated glucose uptake and flux to lactate, is a metabolic hallmark of cancer. Recent studies have identified deuterium (2)H-magnetic resonance spectroscopy (MRS) using 6,6’-(2)H-glucose as a novel method of imaging the Warburg effect in high-grade primary gliob...

Descripción completa

Detalles Bibliográficos
Autores principales: Taglang, Celine, Batsios, Georgios, Tran, Meryssa, Gillepsie, Anne Marie, Luchman, Hema Artee, Pieper, Russell O, Ronen, Sabrina M, Viswanath, Pavithra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992248/
http://dx.doi.org/10.1093/noajnl/vdab024.004
_version_ 1783669334913056768
author Taglang, Celine
Batsios, Georgios
Tran, Meryssa
Gillepsie, Anne Marie
Luchman, Hema Artee
Pieper, Russell O
Ronen, Sabrina M
Viswanath, Pavithra
author_facet Taglang, Celine
Batsios, Georgios
Tran, Meryssa
Gillepsie, Anne Marie
Luchman, Hema Artee
Pieper, Russell O
Ronen, Sabrina M
Viswanath, Pavithra
author_sort Taglang, Celine
collection PubMed
description The Warburg effect, characterized by elevated glucose uptake and flux to lactate, is a metabolic hallmark of cancer. Recent studies have identified deuterium (2)H-magnetic resonance spectroscopy (MRS) using 6,6’-(2)H-glucose as a novel method of imaging the Warburg effect in high-grade primary glioblastomas (GBMs). However, its utility for imaging low-grade gliomas has not been tested. The goal of this study was to determine whether 6,6’-(2)H-glucose can be used for imaging tumor burden and treatment response in mutant isocitrate dehydrogenase (IDHmut) low-grade gliomas in vivo. We examined mice bearing orthotopic tumors of the patient-derived BT257 astrocytoma model. (1)H-MRS, providing a readout of steady-state metabolite levels, confirmed the presence of 2-hydroxyglutarate, the product of IDHmut, in BT257 tumor tissue but not normal brain. Previous studies comparing IDHmut gliomas with GBMs suggest that IDHmut gliomas undergo lactate dehydrogenase silencing, potentially leading to a non-glycolytic phenotype. Nevertheless, our results indicated that, compared to normal brain, glucose uptake and concomitant flux to lactate were significantly higher in BT257 tumor tissue. Importantly, 6,6’-(2)H-glucose metabolism to lactate was observed in BT257 tumor-bearing mice, but not tumor-free mice. Furthermore, imaging studies confirmed spatial localization of lactate production to the tumor vs. contralateral normal brain. We then examined the ability of 6,6’-(2)H-glucose to assess treatment response. Poly-(adenosine 5′-diphosphate-ribose) polymerase inhibitors (PARPi) inhibit IDHmut glioma growth and are in clinical trials for IDHmut glioma patients. Treatment with the PARPi niraparib reduced 6,6’-(2)H-glucose flux to lactate in BT257 tumor-bearing mice. Importantly, this reduction was observed at early time-points when no difference in tumor volume could be detected using anatomical imaging, pointing to the ability of 6,6’-(2)H-glucose to assess pseudoprogression. Collectively, our results suggest that IDHmut gliomas display a glycolytic phenotype amenable to non-invasive (2)H-MRS-based imaging of tumor burden and treatment response.
format Online
Article
Text
id pubmed-7992248
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-79922482021-03-31 BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO Taglang, Celine Batsios, Georgios Tran, Meryssa Gillepsie, Anne Marie Luchman, Hema Artee Pieper, Russell O Ronen, Sabrina M Viswanath, Pavithra Neurooncol Adv Supplement Abstracts The Warburg effect, characterized by elevated glucose uptake and flux to lactate, is a metabolic hallmark of cancer. Recent studies have identified deuterium (2)H-magnetic resonance spectroscopy (MRS) using 6,6’-(2)H-glucose as a novel method of imaging the Warburg effect in high-grade primary glioblastomas (GBMs). However, its utility for imaging low-grade gliomas has not been tested. The goal of this study was to determine whether 6,6’-(2)H-glucose can be used for imaging tumor burden and treatment response in mutant isocitrate dehydrogenase (IDHmut) low-grade gliomas in vivo. We examined mice bearing orthotopic tumors of the patient-derived BT257 astrocytoma model. (1)H-MRS, providing a readout of steady-state metabolite levels, confirmed the presence of 2-hydroxyglutarate, the product of IDHmut, in BT257 tumor tissue but not normal brain. Previous studies comparing IDHmut gliomas with GBMs suggest that IDHmut gliomas undergo lactate dehydrogenase silencing, potentially leading to a non-glycolytic phenotype. Nevertheless, our results indicated that, compared to normal brain, glucose uptake and concomitant flux to lactate were significantly higher in BT257 tumor tissue. Importantly, 6,6’-(2)H-glucose metabolism to lactate was observed in BT257 tumor-bearing mice, but not tumor-free mice. Furthermore, imaging studies confirmed spatial localization of lactate production to the tumor vs. contralateral normal brain. We then examined the ability of 6,6’-(2)H-glucose to assess treatment response. Poly-(adenosine 5′-diphosphate-ribose) polymerase inhibitors (PARPi) inhibit IDHmut glioma growth and are in clinical trials for IDHmut glioma patients. Treatment with the PARPi niraparib reduced 6,6’-(2)H-glucose flux to lactate in BT257 tumor-bearing mice. Importantly, this reduction was observed at early time-points when no difference in tumor volume could be detected using anatomical imaging, pointing to the ability of 6,6’-(2)H-glucose to assess pseudoprogression. Collectively, our results suggest that IDHmut gliomas display a glycolytic phenotype amenable to non-invasive (2)H-MRS-based imaging of tumor burden and treatment response. Oxford University Press 2021-03-25 /pmc/articles/PMC7992248/ http://dx.doi.org/10.1093/noajnl/vdab024.004 Text en © The Author(s) 2021. 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 Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (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 Supplement Abstracts
Taglang, Celine
Batsios, Georgios
Tran, Meryssa
Gillepsie, Anne Marie
Luchman, Hema Artee
Pieper, Russell O
Ronen, Sabrina M
Viswanath, Pavithra
BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO
title BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO
title_full BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO
title_fullStr BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO
title_full_unstemmed BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO
title_short BIMG-05. TO BE OR NOT TO BE GLYCOLYTIC: DEUTERATED GLUCOSE-BASED ASSESSMENT OF THE WARBURG EFFECT ALLOWS NON-INVASIVE IMAGING OF TUMOR BURDEN AND TREATMENT RESPONSE IN MUTANT IDH GLIOMAS IN VIVO
title_sort bimg-05. to be or not to be glycolytic: deuterated glucose-based assessment of the warburg effect allows non-invasive imaging of tumor burden and treatment response in mutant idh gliomas in vivo
topic Supplement Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992248/
http://dx.doi.org/10.1093/noajnl/vdab024.004
work_keys_str_mv AT taglangceline bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT batsiosgeorgios bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT tranmeryssa bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT gillepsieannemarie bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT luchmanhemaartee bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT pieperrussello bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT ronensabrinam bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo
AT viswanathpavithra bimg05tobeornottobeglycolyticdeuteratedglucosebasedassessmentofthewarburgeffectallowsnoninvasiveimagingoftumorburdenandtreatmentresponseinmutantidhgliomasinvivo