Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI
(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe); (...
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4278 |
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| author | Chloé Buyse Nicolas Joudiou Cyril Corbet Olivier Feron Lionel Mignion Julien Flament Bernard Gallez |
| author_facet | Chloé Buyse Nicolas Joudiou Cyril Corbet Olivier Feron Lionel Mignion Julien Flament Bernard Gallez |
| author_sort | Chloé Buyse |
| collection | DOAJ |
| description | (1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe); (2) Methods: glucose consumption, lactate secretion and extracellular acidification rate (ECAR) were measured in vitro after exposure of cervix cancer SiHa cells and breast cancer 4T1 cells to UK-5099 (10 µM). Mice bearing the 4T1 tumor model were treated daily during four days with UK-5099 (3 mg/kg). The pHe was evaluated in vivo using either chemical exchange saturation transfer (CEST)-MRI with iopamidol as pHe reporter probe or <sup>31</sup>P-NMR spectroscopy with 3-aminopropylphosphonate (3-APP). MR protocols were applied before and after 4 days of treatment; (3) Results: glucose consumption, lactate release and ECAR were increased in both cell lines after UK-5099 exposure. CEST-MRI showed a significant decrease in tumor pHe of 0.22 units in UK-5099-treated mice while there was no change over time for mice treated with the vehicle. Parametric images showed a large heterogeneity in response with 16% of voxels shifting to pHe values under 7.0. In contrast, <sup>31</sup>P-NMR spectroscopy was unable to detect any significant variation in pHe; (4) Conclusions: MPC inhibition led to a moderate acidification of the extracellular medium in vivo. CEST-MRI provided high resolution parametric images (0.44 µL/voxel) of pHe highlighting the heterogeneity of response within the tumor when exposed to UK-5099. |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:15:03Z |
| publishDate | 2021-08-01 |
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| series | Cancers |
| spelling | doaj.art-d38d7bf95c5d42f1bcb91483a115f00e2023-11-22T10:24:54ZengMDPI AGCancers2072-66942021-08-011317427810.3390/cancers13174278Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRIChloé Buyse0Nicolas Joudiou1Cyril Corbet2Olivier Feron3Lionel Mignion4Julien Flament5Bernard Gallez6Louvain Drug Research Institute, Biomedical Magnetic Resonance, Université catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumLouvain Drug Research Institute, Nuclear and Electron Spin Technologies (NEST) Platform, Université catholique de Louvain, 1200 Brussels, BelgiumPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumLouvain Drug Research Institute, Biomedical Magnetic Resonance, Université catholique de Louvain (UCLouvain), 1200 Brussels, BelgiumCommissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Molecular Imaging Research Center (MIRCen), Laboratoire des Maladies Neurodégénératives, Université Paris-Saclay, 92265 Fontenay-aux-Roses, FranceLouvain Drug Research Institute, Biomedical Magnetic Resonance, Université catholique de Louvain (UCLouvain), 1200 Brussels, Belgium(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe); (2) Methods: glucose consumption, lactate secretion and extracellular acidification rate (ECAR) were measured in vitro after exposure of cervix cancer SiHa cells and breast cancer 4T1 cells to UK-5099 (10 µM). Mice bearing the 4T1 tumor model were treated daily during four days with UK-5099 (3 mg/kg). The pHe was evaluated in vivo using either chemical exchange saturation transfer (CEST)-MRI with iopamidol as pHe reporter probe or <sup>31</sup>P-NMR spectroscopy with 3-aminopropylphosphonate (3-APP). MR protocols were applied before and after 4 days of treatment; (3) Results: glucose consumption, lactate release and ECAR were increased in both cell lines after UK-5099 exposure. CEST-MRI showed a significant decrease in tumor pHe of 0.22 units in UK-5099-treated mice while there was no change over time for mice treated with the vehicle. Parametric images showed a large heterogeneity in response with 16% of voxels shifting to pHe values under 7.0. In contrast, <sup>31</sup>P-NMR spectroscopy was unable to detect any significant variation in pHe; (4) Conclusions: MPC inhibition led to a moderate acidification of the extracellular medium in vivo. CEST-MRI provided high resolution parametric images (0.44 µL/voxel) of pHe highlighting the heterogeneity of response within the tumor when exposed to UK-5099.https://www.mdpi.com/2072-6694/13/17/4278pHacidosisglycolysistumormitochondrial pyruvate carrier (MPC)MRI |
| spellingShingle | Chloé Buyse Nicolas Joudiou Cyril Corbet Olivier Feron Lionel Mignion Julien Flament Bernard Gallez Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI Cancers pH acidosis glycolysis tumor mitochondrial pyruvate carrier (MPC) MRI |
| title | Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI |
| title_full | Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI |
| title_fullStr | Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI |
| title_full_unstemmed | Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI |
| title_short | Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI |
| title_sort | impact of inhibition of the mitochondrial pyruvate carrier on the tumor extracellular ph as measured by cest mri |
| topic | pH acidosis glycolysis tumor mitochondrial pyruvate carrier (MPC) MRI |
| url | https://www.mdpi.com/2072-6694/13/17/4278 |
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