{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:06:37Z","timestamp":1793192797469,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["J008220F"],"award-info":[{"award-number":["J008220F"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["7463520"],"award-info":[{"award-number":["7463520"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013845","name":"Fondation contre le Cancer","doi-asserted-by":"publisher","award":["2020\/074"],"award-info":[{"award-number":["2020\/074"]}],"id":[{"id":"10.13039\/501100013845","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005043","name":"Fonds Joseph Maisin","doi-asserted-by":"publisher","award":["x"],"award-info":[{"award-number":["x"]}],"id":[{"id":"10.13039\/501100005043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>(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 \u00b5M). 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 31P-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, 31P-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 \u00b5L\/voxel) of pHe highlighting the heterogeneity of response within the tumor when exposed to UK-5099.<\/jats:p>","DOI":"10.3390\/cancers13174278","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:19:26Z","timestamp":1629937166000},"page":"4278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI"],"prefix":"10.3390","volume":"13","author":[{"given":"Chlo\u00e9","family":"Buyse","sequence":"first","affiliation":[{"name":"Louvain Drug Research Institute, Biomedical Magnetic Resonance, Universit\u00e9 catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Joudiou","sequence":"additional","affiliation":[{"name":"Louvain Drug Research Institute, Nuclear and Electron Spin Technologies (NEST) Platform, Universit\u00e9 catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8795-9131","authenticated-orcid":false,"given":"Cyril","family":"Corbet","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5360-0286","authenticated-orcid":false,"given":"Olivier","family":"Feron","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Exp\u00e9rimentale et Clinique (IREC), Universit\u00e9 catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-8600","authenticated-orcid":false,"given":"Lionel","family":"Mignion","sequence":"additional","affiliation":[{"name":"Louvain Drug Research Institute, Biomedical Magnetic Resonance, Universit\u00e9 catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Flament","sequence":"additional","affiliation":[{"name":"Commissariat \u00e0 l\u2019Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Molecular Imaging Research Center (MIRCen), Laboratoire des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, Universit\u00e9 Paris-Saclay, 92265 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Gallez","sequence":"additional","affiliation":[{"name":"Louvain Drug Research Institute, Biomedical Magnetic Resonance, Universit\u00e9 catholique de Louvain (UCLouvain), 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1600200","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci. 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