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While at present there are no effective treatments available, preclinical development and testing of gene therapy and other approaches to increase brain creatine are being actively pursued. In studying a mouse model of the disorder, [<jats:sup>18<\/jats:sup>F]fluorodeoxyglucose ([<jats:sup>18<\/jats:sup>F]FDG)-based positron emission tomography (PET)\/computed tomography (CT) was performed to assess brain glucose metabolism in wild type and creatine transporter mutant mice (<jats:italic>Slc6a8<\/jats:italic>\n            <jats:sup>\n              <jats:italic>-\/y<\/jats:italic>\n            <\/jats:sup>). The findings demonstrate marked differences in glucose metabolism in the brains of wild type and <jats:italic>Slc6a8<\/jats:italic>\n            <jats:sup>\n              <jats:italic>-\/y<\/jats:italic>\n            <\/jats:sup> mice. In conducting behavioral phenotyping studies, notable abnormalities in behavior in the murine model led to additional studies in serotonin-mediated activity. Serotonergic signaling differences were detected between wild type and <jats:italic>Slc6a8<\/jats:italic>\n            <jats:sup>\n              <jats:italic>-\/y<\/jats:italic>\n            <\/jats:sup> mice using 4-(2\u2032-methoxyphenyl)-1-[2\u2032-(<jats:italic>N<\/jats:italic>-2\u2033-pyridinyl)-<jats:italic>p<\/jats:italic>-[<jats:sup>18<\/jats:sup>F]fluorobenzamido]ethylpiperazine ([<jats:sup>18<\/jats:sup>F]MPPF). These data demonstrate that [<jats:sup>18<\/jats:sup>F]FDG-PET and [<jats:sup>18<\/jats:sup>F]-MPPF-PET may serve as appropriate and sensitive biomarkers that could be used to assess the efficacy of not only new approaches in treating mutations of the creatine transporter SLC6A8 and their effectiveness in normalizing brain metabolism but also in enhancing our understanding of the mechanism of brain dysfunction that occurs in this complex brain disorder.<\/jats:p>","DOI":"10.1038\/s41598-025-92022-8","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T09:06:02Z","timestamp":1740819962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["[18F]FDG-PET and [18F]MPPF-PET are brain biomarkers for the creatine transporter Slc6a8 loss of function mutation"],"prefix":"10.1038","volume":"15","author":[{"given":"Isabel","family":"Day","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla","family":"Tamboline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Lueptow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Zhuravka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn","family":"Diep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Tkachyova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shili","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S.","family":"Lipshutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"92022_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1023\/A:1022443503883","volume":"244","author":"A Schulze","year":"2003","unstructured":"Schulze, A. 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