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The resulting loss of Fragile X Mental Retardation Protein (FMRP) leads to excessive glutamate signaling via metabotropic glutamate subtype 5 receptors (mGluR5) which has been implicated in the pathogenesis of the disorder. In the present study we used the radioligand 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([<jats:sup>18<\/jats:sup>F]FPEB) in simultaneous PET-MR imaging of males with FXS and age- and gender-matched controls to assess the availability of mGlu5 receptors in relevant brain areas. Patients with FXS showed lower [<jats:sup>18<\/jats:sup>F]FPEB binding potential (p\u2009&lt;\u2009 0.01), reflecting reduced mGluR5 availability, than the healthy controls throughout the brain, with significant group differences in insula, anterior cingulate, parahippocampal, inferior temporal and olfactory cortices, regions associated with deficits in inhibition, memory, and visuospatial processes characteristic of the disorder. The results are among the first to provide in vivo evidence of decreased availability of mGluR5 in the brain in individuals with FXS than in healthy controls. The consistent results across the subjects, despite the tremendous challenges with neuroimaging this population, highlight the robustness of the protocol and support for its use in drug occupancy studies; extending our radiotracer development and application efforts from mice to humans.<\/jats:p>","DOI":"10.1038\/s41598-021-94967-y","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T10:02:50Z","timestamp":1628157770000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker"],"prefix":"10.1038","volume":"11","author":[{"given":"Maria","family":"Mody","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoann","family":"Petibon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshini","family":"Kuruppu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Yokell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Neelamegam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc D.","family":"Normandin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges El","family":"Fakhri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Liisa","family":"Brownell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"94967_CR1","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-H","volume":"65","author":"AJ Verkerk","year":"1991","unstructured":"Verkerk, A. 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