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Here we characterized and longitudinally assessed the novel radioligand [\n                      <jats:sup>11<\/jats:sup>\n                      C]CHDI-626 for mHTT PET imaging in the zQ175DN mouse model of HD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      After evaluating radiometabolites and radioligand kinetics, we conducted longitudinal dynamic PET imaging at 3, 6, 9, and 13\u00a0months of age (M) in wild-type (WT,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917) and heterozygous (HET,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923) zQ175DN mice. Statistical analysis was performed to evaluate temporal and genotypic differences. Cross-sectional cohorts at each longitudinal time point were included for post-mortem [\n                      <jats:sup>3<\/jats:sup>\n                      H]CHDI-626 autoradiography.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Despite fast metabolism and kinetics, the radioligand was suitable for PET imaging of mHTT. Longitudinal quantification could discriminate between genotypes already at premanifest stage (3\u00a0M), showing an age-associated increase in signal in HET mice in parallel with mHTT aggregate load progression, as supported by the post-mortem [\n                      <jats:sup>3<\/jats:sup>\n                      H]CHDI-626 autoradiography.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      With clinical evaluation underway, [\n                      <jats:sup>11<\/jats:sup>\n                      C]CHDI-626 PET imaging appears to be a suitable preclinical candidate marker to monitor natural HD progression and for the evaluation of mHTT-lowering therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-021-05578-8","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T02:41:59Z","timestamp":1634265719000},"page":"1166-1175","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Longitudinal preclinical evaluation of the novel radioligand [11C]CHDI-626 for PET imaging of mutant huntingtin aggregates in Huntington\u2019s disease"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-5432","authenticated-orcid":false,"given":"Daniele","family":"Bertoglio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen","family":"Verhaeghe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Wyffels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigrid","family":"Stroobants","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ladislav","family":"Mrzljak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod","family":"Khetarpal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"Skinbjerg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longbin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Munoz-Sanjuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Bard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Staelens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"issue":"6","key":"5578_CR1","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","volume":"72","author":"The Huntington\u2019s Disease Collaborative Research Group","year":"1993","unstructured":"The Huntington\u2019s Disease Collaborative Research Group. 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