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In this study, two human prostate cancer cell lines, PC3 and LNCaP, have been treated in vitro with proton pump inhibitors (PPIs), namely Lansoprazole, Esomeprazole (V-ATPases-inhibitors), Cariporide, and Amiloride (NHE1-inhibitors). The cell viability and pH were assessed at several drug concentrations either at normoxic or hypoxic conditions. Since Esomeprazole showed the highest toxicity towards the PC3 cancer cells compared to LNCaP ones, athymic nude mice bearing subcutaneous or orthotopic PC3 tumors were treated with Esomeprazole (dose: 2.5 mg\/kg body weight) for a period of three weeks\u2014and tumor growth was monitored. MRI-CEST tumor pH imaging with Iopamidol was performed upon treatment at 3 h, 1 week (in combination with FDG-PET), and after 2 weeks for evaluating acute, early, and late responses. Although acute tumor pH changes were observed in vivo, long-term studies on both PC3 prostate cancer models did not provide any significant change in tumor acidosis or tumor growth. In conclusion, this work shows that MRI-CEST tumor pH imaging is a valuable tool for assessing the in vivo treatment response to PPIs.<\/jats:p>","DOI":"10.3390\/cancers14194916","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"4916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["In Vivo MRI-CEST Tumor pH Imaging Detects Resistance to Proton Pump Inhibitors in Human Prostate Cancer Murine Models"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-6523","authenticated-orcid":false,"given":"Pietro","family":"Irrera","sequence":"first","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Consolino","sequence":"additional","affiliation":[{"name":"Department of Nanomedicines and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3804-5031","authenticated-orcid":false,"given":"Miriam","family":"Roberto","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9125-8004","authenticated-orcid":false,"given":"Martina","family":"Capozza","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Dhakan","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Carella","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Corrado","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Villano","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annasofia","family":"Anemone","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Navarro-Tableros","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Bracesco","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Dastr\u00f9","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Aime","sequence":"additional","affiliation":[{"name":"IRCCS SDN SynLab, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-9925","authenticated-orcid":false,"given":"Dario Livio","family":"Longo","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why do cancers have high aerobic glycolysis?","volume":"4","author":"Gatenby","year":"2004","journal-title":"Nat. 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