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In this study, we assessed in vivo pathological changes in mGluR1 availability in the Q175DN mouse model of HD using longitudinal positron emission tomography (PET) imaging with the radioligand [<jats:sup>11<\/jats:sup>C]ITDM. Ninety-minute dynamic PET imaging scans were performed in 22 heterozygous (HET) Q175DN mice and 22 wild-type (WT) littermates longitudinally at 6, 12, and 16\u00a0months of age. Analyses of regional volume of distribution with an image-derived input function (<jats:italic>V<\/jats:italic><jats:sub>T (IDIF)<\/jats:sub>) and voxel-wise parametric <jats:italic>V<\/jats:italic><jats:sub>T (IDIF)<\/jats:sub> maps were performed to assess differences between genotypes. <jats:italic>Post-mortem<\/jats:italic> evaluation at 16\u00a0months was done to support in vivo findings. [<jats:sup>11<\/jats:sup>C]ITDM <jats:italic>V<\/jats:italic><jats:sub>T (IDIF)<\/jats:sub> quantification revealed higher mGluR1 availability in the brain of HET mice compared to WT littermates (e.g. cerebellum: +\u200915.0%, +\u200917.9%, and +\u200917.6% at 6, 12, and 16\u00a0months, respectively; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In addition, an age-related decline in [<jats:sup>11<\/jats:sup>C]ITDM binding independent of genotype was observed between 6 and 12\u00a0months. Voxel-wise analysis of parametric maps and <jats:italic>post-mortem<\/jats:italic> quantifications confirmed the elevated mGluR1 availability in HET mice compared to WT\u00a0littermates. In conclusion, in vivo measurement of mGluR1 availability using longitudinal [<jats:sup>11<\/jats:sup>C]ITDM PET imaging demonstrated higher [<jats:sup>11<\/jats:sup>C]ITDM binding in extra-striatal brain regions during the course of disease in the Q175DN mouse model.<\/jats:p>","DOI":"10.1007\/s12035-019-01866-5","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T03:02:30Z","timestamp":1578452550000},"page":"2038-2047","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Elevated Type 1 Metabotropic Glutamate Receptor Availability in a Mouse Model of Huntington\u2019s Disease: a Longitudinal PET Study"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-5432","authenticated-orcid":false,"given":"Daniele","family":"Bertoglio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Verhaeghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0160pela","family":"Korat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Cybulska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Wyffels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Stroobants","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Mrzljak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Skinbjerg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longbin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Munoz-Sanjuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Staelens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"issue":"4","key":"1866_CR1","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1124\/pr.108.000166","volume":"60","author":"F Ferraguti","year":"2008","unstructured":"Ferraguti F, Crepaldi L, Nicoletti F (2008) Metabotropic glutamate 1 receptor: Current concepts and perspectives. 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LM, CD, LL, MS, IMS are employees of CHDI foundation, Inc. The authors declare no other potential conflicts of interest relevant to this work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All applicable institutional and\/or national guidelines for the care and use of animals were followed. Experiments were performed according to the European Committee Guidelines (decree 2010\/63\/CEE) and the Animal Welfare Act (7 USC 2131), and they were approved by the Ethical Committee for Animal Testing (ECD 2017\u201327) at the University of Antwerp (Belgium).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}