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Only two fluorinated C24H-targeting PET radioligands, [\u00b9\u2078F]CHL-2205 and [\u00b9\u2078F]T008, have recently entered clinical use. Direct comparison is needed to guide radiotracer selection for future translational studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Dynamic PET imaging was performed using either [\u00b9\u2078F]CHL-2205 or [\u00b9\u2078F]T008 in parallel conditions in cynomolgus macaques, healthy rats, the TgF344-AD rat model, and C24H-overexpressing mice. Arterial blood sampling enabled full kinetic modeling in healthy rats and nonhuman primates. An image-derived input function was validated in rats, and the specific binding was evaluated under C24H saturation using soticlestat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\u00b9\u2078F]CHL-2205 and [\u00b9\u2078F]T008 showed similar metabolism profiles in either macaques or rats. In macaques, brain uptake values (\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>T<\/jats:sub>\n                      , Logan plot analysis) were 1.6-fold higher for [\u00b9\u2078F]CHL-2205 relative to [\u00b9\u2078F]T008. Healthy rats showed a similar pattern, with [\u00b9\u2078F]CHL-2205 exhibiting 1.5-fold higher brain\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>T<\/jats:sub>\n                      . In rats, soticlestat blockade revealed C24H-specific binding for both ligands, with an estimated binding potential (BPND) 1.3-fold higher for [\u00b9\u2078F]CHL-2205 compared to [\u00b9\u2078F]T008. In TgF344-AD rats, brain uptake increased by 1.9-fold with [\u00b9\u2078F]CHL-2205 versus 1.6-fold with [\u00b9\u2078F]T008 compared to wild-type controls. In C24H-overexpressing mice, [\u00b9\u2078F]CHL-2205 detected measurable increases in brain signal in several brain regions (up to 1.5-fold), while [\u00b9\u2078F]T008 did not in the same animals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Across species and models, both radioligands demonstrated appropriate characteristics for imaging C24H in vivo. However, [\u00b9\u2078F]CHL-2205 generally displayed higher specific binding and appeared more sensitive to detect moderate increases in C24H expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-07937-9","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:59:51Z","timestamp":1780127991000},"page":"6154-6166","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Head-to-head comparison of [18F]CHL2205 versus [18F]T008 as PET radioligands to study brain cholesterol homeostasis in rodent models and nonhuman primates"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-0740","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Goutal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-7337","authenticated-orcid":false,"given":"Fabien","family":"Caille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3516-3873","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Piguet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-345X","authenticated-orcid":false,"given":"Maud","family":"Goislard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Amargier-Barrial","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2279-9743","authenticated-orcid":false,"given":"Sarah","family":"Leterrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5247-4871","authenticated-orcid":false,"given":"Sol\u00e8ne","family":"Marie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-3653","authenticated-orcid":false,"given":"Michel","family":"Bottlaender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-2030","authenticated-orcid":false,"given":"Nicolas","family":"Tournier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"7937_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1038\/s12276-024-01273-4","volume":"56","author":"KC Shin","year":"2024","unstructured":"Shin KC, Ali Moussa HY, Park Y. 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The experimental protocol was evaluated and approved by a local ethics committee for animal use and sanctioned by the French government (approval numbers APAFIS #44238-2023072111212158 v2 for rodents and APAFIS #41733-2023031614569134 v1 for non-human primates). The animal experiment data reported in this study comply with the ARRIVE 2.0 (Animal Research: Reporting in Vivo Experiments) guidelines.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}