{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:25:35Z","timestamp":1767900335015,"version":"3.49.0"},"reference-count":54,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"630","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,2,2]]},"abstract":"<jats:p>\n            Huntington\u2019s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin (\n            <jats:italic>HTT<\/jats:italic>\n            ) gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (polyQ) tract. Whereas several therapeutic programs targeting mHTT expression have advanced to clinical evaluation, methods to visualize mHTT protein species in the living brain are lacking. Here, we demonstrate the development and characterization of a positron emission tomography (PET) imaging radioligand with high affinity and selectivity for mHTT aggregates. This small molecule radiolabeled with\n            <jats:sup>11<\/jats:sup>\n            C ([\n            <jats:sup>11<\/jats:sup>\n            C]CHDI-180R) allowed noninvasive monitoring of mHTT pathology in the brain and could track region- and time-dependent suppression of mHTT in response to therapeutic interventions targeting mHTT expression in a rodent model. We further showed that in these animals, therapeutic agents that lowered mHTT in the striatum had a functional restorative effect that could be measured by preservation of striatal imaging markers, enabling a translational path to assess the functional effect of mHTT lowering.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abm3682","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T18:53:15Z","timestamp":1643827995000},"source":"Crossref","is-referenced-by-count":39,"title":["Development of a ligand for in vivo imaging of mutant huntingtin in Huntington\u2019s disease"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-5432","authenticated-orcid":true,"given":"Daniele","family":"Bertoglio","sequence":"first","affiliation":[{"name":"Molecular Imaging Center Antwerp (MICA), University of Antwerp, Wilrijk 2610, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5097-1361","authenticated-orcid":true,"given":"Jonathan","family":"Bard","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation, Los Angeles, CA 90045, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Hessmann","sequence":"additional","affiliation":[{"name":"Evotec SE, Hamburg 22419, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-0196","authenticated-orcid":true,"given":"Longbin","family":"Liu","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation, Los Angeles, CA 90045, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Evotec SE, Hamburg 22419, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5307-3575","authenticated-orcid":true,"given":"Stef","family":"De Lombaerde","sequence":"additional","affiliation":[{"name":"Molecular Imaging Center Antwerp (MICA), University of Antwerp, Wilrijk 2610, Belgium."},{"name":"Department of Nuclear Medicine, Antwerp University Hospital, Edegem 2650, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Huscher","sequence":"additional","affiliation":[{"name":"Evotec SE, Hamburg 22419, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Zajicek","sequence":"additional","affiliation":[{"name":"Molecular Imaging Center Antwerp (MICA), University of Antwerp, Wilrijk 2610, 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Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-3966","authenticated-orcid":true,"given":"Tamara","family":"Vasilkovska","sequence":"additional","affiliation":[{"name":"Bio-Imaging Lab, University of Antwerp, Wilrijk 2610, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Evotec Ltd., Abingdon OX14 4RZ, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-6233","authenticated-orcid":true,"given":"Peter D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Evotec Ltd., Abingdon OX14 4RZ, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-6885","authenticated-orcid":true,"given":"Michael E.","family":"Prime","sequence":"additional","affiliation":[{"name":"Evotec Ltd., Abingdon OX14 4RZ, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Mills","sequence":"additional","affiliation":[{"name":"Evotec Ltd., Abingdon OX14 4RZ, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2941-6520","authenticated-orcid":true,"given":"Annemie","family":"Van der Linden","sequence":"additional","affiliation":[{"name":"Bio-Imaging Lab, University of Antwerp, Wilrijk 2610, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5777-1354","authenticated-orcid":true,"given":"Ladislav","family":"Mrzljak","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation, Los Angeles, CA 90045, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-5117","authenticated-orcid":true,"given":"Vinod","family":"Khetarpal","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI 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S.","year":"2020","unstructured":"N. S. Caron, A. L. Southwell, C. C. Brouwers, L. D. Cengio, Y. Xie, H. F. Black, L. M. Anderson, S. Ko, X. Zhu, S. J. van Deventer, M. M. Evers, P. Konstantinova, M. R. Hayden, Potent and sustained huntingtin lowering via AAV5 encoding miRNA preserves striatal volume and cognitive function in a humanized mouse model of Huntington disease. Nucleic Acids Res. 48, 36\u201354 (2020).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10776"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.107"},{"key":"e_1_3_3_43_2","article-title":"Synaptic vesicle glycoprotein 2A is affected in the CNS of Huntington\u2019s disease mice and post-mortem human HD brain","author":"Bertoglio D.","unstructured":"D. Bertoglio, J. Verhaeghe, L. Wyffels, A. Miranda, S. Stroobants, L. Mrzljak, C. Dominguez, M. Skinbjerg, J. Bard, L. Liu, I. Munoz-Sanjuan, S. 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