{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:41:22Z","timestamp":1762299682253,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","award":["7211172142"],"award-info":[{"award-number":["7211172142"]}],"id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [18F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [18F]FACH in healthy mice and piglets. We measured the [18F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [18F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET\/MRI in vivo, with and without pre-treatment by the MCT inhibitor \u03b1-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a KD of 118 \u00b1 12 nM and Bmax of 6.0 pmol\/mg wet weight. The specificity of [18F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC0\u201360min after pre-treatment with \u03b1-CCA-Na in mice (\u221247%) and in piglets (\u221266%). [18F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [18F]FACH binding potential (BPND) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [18F]FACH uptake was confirmed by displacement studies in 4T1 cells. [18F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.<\/jats:p>","DOI":"10.3390\/ijms22041645","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T20:51:51Z","timestamp":1612817511000},"page":"1645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-2325","authenticated-orcid":false,"given":"Daniel","family":"G\u00fcndel","sequence":"first","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6844-6637","authenticated-orcid":false,"given":"Masoud","family":"Sadeghzadeh","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3062","authenticated-orcid":false,"given":"Winnie","family":"Deuther-Conrad","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7390-3575","authenticated-orcid":false,"given":"Barbara","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Cumming","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University, 3010 Bern, Switzerland"},{"name":"School of Psychology and Counselling, Queensland University of Technology, Brisbane 4000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-3857","authenticated-orcid":false,"given":"Magali","family":"Toussaint","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-5171","authenticated-orcid":false,"given":"Friedrich-Alexander","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-7945","authenticated-orcid":false,"given":"Rare\u015f-Petru","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5641-7396","authenticated-orcid":false,"given":"Mathias","family":"Kranz","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-0567","authenticated-orcid":false,"given":"Rodrigo","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-2609","authenticated-orcid":false,"given":"Bernhard","family":"Sattler","sequence":"additional","affiliation":[{"name":"Department for Nuclear Medicine, University Hospital Leipzig, 04103 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama","family":"Sabri","sequence":"additional","affiliation":[{"name":"Department for Nuclear Medicine, University Hospital Leipzig, 04103 Leipzig, Saxony, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-7058","authenticated-orcid":false,"given":"Peter","family":"Brust","sequence":"additional","affiliation":[{"name":"Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, 04308 Leipzig, Saxony, 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