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Due to its high efficacy agonist properties, [\n                      <jats:sup>18<\/jats:sup>\n                      F]F13640 binds preferentially to functional 5-HT\n                      <jats:sub>1A<\/jats:sub>\n                      receptors, which are coupled to intracellular G-proteins. Here, we characterize brain labeling of 5-HT\n                      <jats:sub>1A<\/jats:sub>\n                      receptors by [\n                      <jats:sup>18<\/jats:sup>\n                      F]F13640 in humans and describe a simplified model for its quantification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PET\/CT and PET-MRI scans were conducted in a total of 13 healthy male volunteers (29\u2009\u00b1\u20099\u00a0years old), with arterial input functions (AIF) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099) and test\u2013retest protocol (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098). Several kinetic models were compared (one tissue compartment model, two-tissue compartment model, and Logan); two models with reference region were also evaluated: simplified reference tissue model (SRTM) and the logan reference model (LREF).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]F13640 showed high uptake values in raphe nuclei and cortical regions. SRTM and LREF models showed a very high correlation with kinetic models using AIF. As concerns test\u2013retest parameters and the prolonged binding kinetics of [\n                      <jats:sup>18<\/jats:sup>\n                      F]F13640, better reproducibility, and reliability were found with the LREF method. Cerebellum white matter and frontal lobe white matter stand out as suitable reference regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The favorable brain labeling and kinetic profile of [\n                      <jats:sup>18<\/jats:sup>\n                      F]F13640, its high receptor specificity and its high efficacy agonist properties open new perspectives for studying functionally active 5-HT\n                      <jats:sub>1A<\/jats:sub>\n                      receptors, unlike previous radiopharmaceuticals that act as antagonists. [\n                      <jats:sup>18<\/jats:sup>\n                      F]F13640\u2019s kinetic properties allow injection outside of the PET scanner with delayed acquisitions, facilitating the design of innovative longitudinal protocols in neurology and psychiatry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration.<\/jats:title>\n                    <jats:p>Trial Registration EudraCT 2017\u2013002,722-21.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-022-06103-1","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T03:04:35Z","timestamp":1674097475000},"page":"1651-1664","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["[18F]F13640: a selective agonist PET radiopharmaceutical for imaging functional 5-HT1A receptors in humans"],"prefix":"10.1007","volume":"50","author":[{"given":"Pierre","family":"Courault","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lancelot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Costes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Colom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Le Bars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Redoute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Gobert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Dailler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibel","family":"Isal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Iecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Newman-Tancredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Merida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-7098","authenticated-orcid":false,"given":"Luc","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"6103_CR1","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1016\/j.cellsig.2010.03.019","volume":"22","author":"AM Polter","year":"2010","unstructured":"Polter AM, Li X. 5-HT1A receptor-regulated signal transduction pathways in brain. 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