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Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI)
INTRODUCTION: There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175635/ https://www.ncbi.nlm.nih.gov/pubmed/37187610 http://dx.doi.org/10.3389/fncel.2023.1130816 |
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author | Ip, Kevan L. Thomas, Monique A. Behar, Kevin L. de Graaf, Robin A. De Feyter, Henk M. |
author_facet | Ip, Kevan L. Thomas, Monique A. Behar, Kevin L. de Graaf, Robin A. De Feyter, Henk M. |
author_sort | Ip, Kevan L. |
collection | PubMed |
description | INTRODUCTION: There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to-brain image contrast. METHODS: RG2 cells were incubated with choline and the level of intracellular choline and its metabolites measured in cell extracts using high resolution (1)H NMR. In rats with orthotopically implanted RG2 tumors deuterium metabolic imaging (DMI) was applied in vivo during, as well as 1 day after, intravenous infusion of (2)H(9)-choline. In parallel experiments, RG2-bearing rats were infused with [1,1′,2,2′-(2)H(4)]-choline and tissue metabolite extracts analyzed with high resolution (2)H NMR to identify molecule-specific (2)H-labeling in choline and its metabolites. RESULTS: In vitro experiments indicated high uptake and fast phosphorylation of exogenous choline in RG2 cells. In vivo DMI studies revealed a high signal from the (2)H-labeled pool of choline + metabolites (total choline, (2)H-tCho) in the tumor lesion but not in normal brain. Quantitative DMI-based metabolic maps of (2)H-tCho showed high tumor-to-brain image contrast in maps acquired both during, and 24 h after deuterated choline infusion. High resolution (2)H NMR revealed that DMI data acquired during (2)H-choline infusion consists of free choline and phosphocholine, while the data acquired 24 h later represent phosphocholine and glycerophosphocholine. DISCUSSION: Uptake and metabolism of exogenous choline was high in RG2 tumors compared to normal brain, resulting in high tumor-to-brain image contrast on DMI-based metabolic maps. By varying the timing of DMI data acquisition relative to the start of the deuterated choline infusion, the metabolic maps can be weighted toward detection of choline uptake or choline metabolism. These proof-of-principle experiments highlight the potential of using deuterated choline combined with DMI to metabolically characterize brain tumors. |
format | Online Article Text |
id | pubmed-10175635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101756352023-05-13 Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) Ip, Kevan L. Thomas, Monique A. Behar, Kevin L. de Graaf, Robin A. De Feyter, Henk M. Front Cell Neurosci Neuroscience INTRODUCTION: There is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to-brain image contrast. METHODS: RG2 cells were incubated with choline and the level of intracellular choline and its metabolites measured in cell extracts using high resolution (1)H NMR. In rats with orthotopically implanted RG2 tumors deuterium metabolic imaging (DMI) was applied in vivo during, as well as 1 day after, intravenous infusion of (2)H(9)-choline. In parallel experiments, RG2-bearing rats were infused with [1,1′,2,2′-(2)H(4)]-choline and tissue metabolite extracts analyzed with high resolution (2)H NMR to identify molecule-specific (2)H-labeling in choline and its metabolites. RESULTS: In vitro experiments indicated high uptake and fast phosphorylation of exogenous choline in RG2 cells. In vivo DMI studies revealed a high signal from the (2)H-labeled pool of choline + metabolites (total choline, (2)H-tCho) in the tumor lesion but not in normal brain. Quantitative DMI-based metabolic maps of (2)H-tCho showed high tumor-to-brain image contrast in maps acquired both during, and 24 h after deuterated choline infusion. High resolution (2)H NMR revealed that DMI data acquired during (2)H-choline infusion consists of free choline and phosphocholine, while the data acquired 24 h later represent phosphocholine and glycerophosphocholine. DISCUSSION: Uptake and metabolism of exogenous choline was high in RG2 tumors compared to normal brain, resulting in high tumor-to-brain image contrast on DMI-based metabolic maps. By varying the timing of DMI data acquisition relative to the start of the deuterated choline infusion, the metabolic maps can be weighted toward detection of choline uptake or choline metabolism. These proof-of-principle experiments highlight the potential of using deuterated choline combined with DMI to metabolically characterize brain tumors. Frontiers Media S.A. 2023-04-28 /pmc/articles/PMC10175635/ /pubmed/37187610 http://dx.doi.org/10.3389/fncel.2023.1130816 Text en Copyright © 2023 Ip, Thomas, Behar, de Graaf and De Feyter. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Ip, Kevan L. Thomas, Monique A. Behar, Kevin L. de Graaf, Robin A. De Feyter, Henk M. Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) |
title | Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) |
title_full | Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) |
title_fullStr | Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) |
title_full_unstemmed | Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) |
title_short | Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI) |
title_sort | mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (dmi) |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175635/ https://www.ncbi.nlm.nih.gov/pubmed/37187610 http://dx.doi.org/10.3389/fncel.2023.1130816 |
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