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We report the binding specificity of an S1PR1 PET radiotracer, [\n                    <jats:sup>18<\/jats:sup>\n                    F]TZ82112, via in\u00a0vitro autoradiography blocking studies with S1PR1 modulators in human and rat brain tissues and evaluate the tracer kinetics via kinetic modeling in nonhuman primates (NHPs) to assess its potential for clinical translation. A total of 12 scans were performed in four male macaques (M 1\u20134). Each macaque had 1\u20134 baseline scans and at least one blocking scan in three macaques. Arterial input function (AIF) was obtained from M2 and M3 under baseline conditions and M3 after pretreatment with cold TZ82112. The metabolite\u2010corrected plasma AIF was applied to several kinetic models\u2014one\u2010tissue compartment (1TC) and 2TC, and Graphical Logan Analysis. Five candidate reference regions, namely the whole cerebellum, brain stem, occipital cortex, corpus callosum, and cerebral white matter, were investigated for deriving the standardized uptake value ratios (\n                    <jats:italic>SUVr<\/jats:italic>\n                    ). The 2TC with four parameters (2TC4K) with blood volume (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>b<\/jats:sub>\n                    ) fitting is the most suitable kinetic model for evaluating [\n                    <jats:sup>18<\/jats:sup>\n                    F]TZ82112 kinetics. Pretreatment with unlabeled TZ82112 reduced uptake of [\n                    <jats:sup>18<\/jats:sup>\n                    F]TZ82112, demonstrating specific binding in all analyzed regions, including potential reference regions. Reduced tracer uptake in in\u00a0vitro blocking studies further confirmed the tracer specificity to S1PR1. We concluded that accurate [\n                    <jats:sup>18<\/jats:sup>\n                    F]TZ82112 quantification requires AIF measurements, owing to the lack of a suitable reference region; no reference region modeling approach or\n                    <jats:italic>SUVr<\/jats:italic>\n                    would be appropriate. Fast tracer uptake and high\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    values, particularly in the prefrontal cortex and striatum, indicated that [\n                    <jats:sup>18<\/jats:sup>\n                    F]TZ82112 enters the brain quickly and has high S1PR1\u2010specific binding in NHP brain. The current findings further support [\n                    <jats:sup>18<\/jats:sup>\n                    F]TZ82112 as a good PET radiotracer for the quantification of S1PR1 in the brain, provided an AIF is employed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70447-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70447","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:04:01Z","timestamp":1777017841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kinetic Modeling of a Novel Putative Sphingosine\u20101\u2010Phosphate Receptor 1 (\n                    <scp>S<\/scp>\n                    1\n                    <scp>PR<\/scp>\n                    1) Radiotracer [\n                    <sup>18<\/sup>\n                    <scp>F<\/scp>\n                    ]\n                    <scp>TZ<\/scp>\n                    82112 in Nonhuman Primates"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-8785","authenticated-orcid":false,"given":"Ying\u2010Hwey","family":"Nai","sequence":"first","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8823-4132","authenticated-orcid":false,"given":"Lin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8845-4378","authenticated-orcid":false,"given":"Hao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham Z.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"},{"name":"Department of Neurology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2269-6267","authenticated-orcid":false,"given":"John J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-8367","authenticated-orcid":false,"given":"Dean F.","family":"Wong","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"},{"name":"Department of Neurology Washington University School of Medicine  St Louis Missouri USA"},{"name":"Department of Psychiatry Washington University School of Medicine  St Louis Missouri USA"},{"name":"Department of Neuroscience Washington University School of Medicine  St Louis Missouri USA"},{"name":"Department of Neurosurgery University of Maryland Baltimore School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-4901","authenticated-orcid":false,"given":"Tianyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6550-0570","authenticated-orcid":false,"given":"Robert","family":"Gropler","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-0552","authenticated-orcid":false,"given":"Tammie L. 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