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[<jats:sup>11<\/jats:sup>C]PiB has been widely used for imaging \u03b2-amyloid plaques due to its high affinity and selectivity for amyloid deposits. [<jats:sup>18<\/jats:sup>F]AZD4694 is a more recently developed amyloid-PET imaging agent, which structurally resembles PiB and has less non-specific binding in the white matter than other <jats:sup>18<\/jats:sup>F-labeled compounds. The purpose of this study is to compare the in vitro binding properties of the amyloid-PET radiotracers [<jats:sup>11<\/jats:sup>C]PiB and [<jats:sup>18<\/jats:sup>F]AZD4694 in <jats:italic>post-mortem<\/jats:italic> human brain tissue. Total binding was assessed by autoradiography in prefrontal, inferior parietal, posterior cingulate cortices and hippocampal sections of healthy control (HC) and AD autopsy-confirmed brain tissues. Furthermore, the displacement of [<jats:sup>18<\/jats:sup>F]AZD4694 by unlabeled PiB was evaluated in the above-mentioned sections of AD brain tissues.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>For both radiotracers, we found significant differences (p\u2009&lt;\u20090.0001) between HC and AD tissues binding in the prefrontal cortex ([<jats:sup>11<\/jats:sup>C]PiB Cohen\u2019s d\u2009=\u20093.424, [<jats:sup>18<\/jats:sup>F]AZD4694 Cohen\u2019s d\u2009=\u20095.070), inferior parietal cortex ([<jats:sup>11<\/jats:sup>C]PiB Cohen\u2019s d\u2009=\u20093.156, [<jats:sup>18<\/jats:sup>F]AZD4694 Cohen\u2019s d\u2009=\u20093.959), posterior cingulate cortex ([<jats:sup>11<\/jats:sup>C]PiB Cohen\u2019s d\u2009=\u20091.781, [<jats:sup>18<\/jats:sup>F]AZD4694 Cohen\u2019s d\u2009=\u20093.434), and hippocampus ([<jats:sup>11<\/jats:sup>C]PiB Cohen\u2019s d\u2009=\u20091.320, [<jats:sup>18<\/jats:sup>F]AZD4694 Cohen\u2019s d\u2009=\u20093.696). Higher binding was detected for [<jats:sup>18<\/jats:sup>F]AZD4694 compared to [<jats:sup>11<\/jats:sup>C]PiB in AD prefrontal, inferior parietal and posterior cingulate cortices, while binding in the hippocampus was comparable for both radioligands. Strong correlations between [<jats:sup>18<\/jats:sup>]AZD4694 and [<jats:sup>11<\/jats:sup>C]PiB were found in the prefrontal (R\u2009=\u20090.959, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), inferior parietal (R\u2009=\u20090.893, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), posterior cingulate (R\u2009=\u20090.838, <jats:italic>p<\/jats:italic>\u2009=\u20090.0006) cortices and hippocampus (R\u2009=\u20090.750, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Bland\u2013Altman analyses revealed strong agreement between [<jats:sup>11<\/jats:sup>C]PiB and [<jats:sup>18<\/jats:sup>F]AZD4694 in the prefrontal, inferior parietal, and posterior cingulate cortices, but lower agreement in the hippocampus. Displacement studies confirmed high binding affinity of PiB in all tissues, indicating that both amyloid-PET agents compete for the same binding sites.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This head-to-head study provides evidence that while [<jats:sup>18<\/jats:sup>F]AZD4694 and [<jats:sup>11<\/jats:sup>C]PiB bindings are highly correlated with both tracers competing for the same binding sites, [<jats:sup>18<\/jats:sup>F]AZD4694 has a slightly higher effect size when comparing between neuropathologically-confirmed AD and HC brain tissues.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13550-025-01216-8","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T06:12:10Z","timestamp":1743487930000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Autoradiographic comparison between 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According to institutional procedures for autopsy consents for post-mortem tissue, the patients\/participants provided their consent to participate in this study with their written information.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"According to institutional procedures for autopsy consents for post-mortem tissue, the patients\/participants provided informed consent for publication of the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JT has received consultancy fees from the Neurotorium educational platform and from Alzheon Inc, outside the scope of the present work. PR-N has served at scientific advisory boards and\/or as a consultant for Roche, Novo Nordisk, Eisai, and Cerveau radiopharmaceuticals. ERZ has served on the scientific advisory board of Nintx, Novo Nordisk and Masima. He is also a co-founder and a minority shareholder at Masima. All other authors report no disclosures.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"30"}}