{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:30:46Z","timestamp":1773675046338,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR-375870"],"award-info":[{"award-number":["CIHR-375870"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada First Research Excellence Fund (BrainsCAN)","award":["CIHR-375870"],"award-info":[{"award-number":["CIHR-375870"]}]},{"name":"Brain Canada Platform Support Grant","award":["CIHR-375870"],"award-info":[{"award-number":["CIHR-375870"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Acidification of cancerous tissue induced pharmacologically may slow tumor growth and can be detected using magnetic resonance imaging. Numerous studies have shown that pharmacologically inhibiting specific transporters, such as the Na+\/H+ exchanger 1 (NHE1), can alter glycolitic metabolism and affect tumor acidosis. The sodium proton exchanger inhibitor Cariporide can acidify U87MG gliomas in mice. This study aimed to determine whether Cariporide could acidify C6 glioma tumors in rats with an intact immune system. C6 glioma cells were implanted in the right brain hemisphere of ten rats. Chemical exchange saturation transfer (CEST) MRI (9.4T) was acquired on days 7\u20138 and 14\u201315 after implantation to measure in vivo tissue intracellular pH (pHi) within the tumors and on the contralateral side. pHi was basic relative to contralateral tissue at both time points assessed using the amine and amide concentration-independent detection (AACID) value. On day 14\u201315, measurements were made before and up to 160 min after Cariporide injection (N = 6). Twenty minutes after drug injection, the average AACID value in the tumor significantly increased by \u223c6.4% compared to pre-injection, corresponding to 0.31 \u00b1 0.20 lower pHi, while in contralateral tissue, AACID value increased significantly by \u223c4.3% compared to pre-injection, corresponding to 0.22 \u00b1 0.19 lower pHi. Control rats without tumors showed no changes following injection of Cariporide dissolved in 10% or 1% DMSO and diluted in PBS. This study demonstrates the sensitivity of CEST-based pH-weighted imaging for monitoring the response of tumors to pharmacologically induced acidification.<\/jats:p>","DOI":"10.3390\/metabo13070823","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:54:41Z","timestamp":1688604881000},"page":"823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intracellular Acidification in a Rat C6 Glioma Model following Cariporide Injection Investigated by CEST-MRI"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5774-8727","authenticated-orcid":false,"given":"Maryam","family":"Mozaffari","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Centre for Functional and Metabolic Mapping, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-6060","authenticated-orcid":false,"given":"Nivin N.","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Functional and Metabolic Mapping, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Bellyou","sequence":"additional","affiliation":[{"name":"Centre for Functional and Metabolic Mapping, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-363X","authenticated-orcid":false,"given":"Timothy J.","family":"Scholl","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada"},{"name":"Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7118-9096","authenticated-orcid":false,"given":"Robert","family":"Bartha","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Centre for Functional and Metabolic Mapping, Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17556","DOI":"10.1038\/s41598-017-17752-w","article-title":"Immune microenvironment of experimental rat C6 gliomas resembles human glioblastomas","volume":"7","author":"Gieryng","year":"2017","journal-title":"Sci. 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