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Positron emission tomography (PET) with tracers targeting the translocator protein (TSPO) enables the in vivo quantification of microgliosis. TSPO tracers have shown similar disease-specific patterns across cohorts. However, direct quantitative comparisons between commonly used TSPO-PET tracers in tauopathies have not been performed. Here, we apply a TSPO-PET standardization pipeline across clinically matched AD cohorts and PSP cohorts, to quantify, compare and combine multi-centre TSPO-PET data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with PSP were scanned with either [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195 or [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE-180 at one of two centres, while patients with AD and control participants were scanned with either [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195, [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE-180 or [\n                      <jats:sup>11<\/jats:sup>\n                      C]PBR28 at one of three centres. A standardised pre-processing pipeline was implemented and participant standardised uptake volume ratio (SUVR) values were z-scored using tracer-specific control participant values. In a data-driven approach, dissimilarity analyses were employed to assess differences between tracers across clinically matched cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In PSP, dissimilarity analysis suggested that [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195 and [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE-180 binding patterns were comparable following standardisation. In AD, comparability across tracers was less robust, with [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195 and [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE-180 being most comparable, followed by [\n                      <jats:sup>18<\/jats:sup>\n                      F]GE-180 vs. [\n                      <jats:sup>11<\/jats:sup>\n                      C]PBR28, then by [\n                      <jats:sup>11<\/jats:sup>\n                      C]PK11195 vs. [\n                      <jats:sup>11<\/jats:sup>\n                      C]PBR28.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The pipeline was effective at harmonising TSPO-PET tracers and standardising the regional quantification of neuroinflammation in clinically matched cohorts of PSP, while the standardisation pipeline results were less robust across AD cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07579-3","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T07:15:10Z","timestamp":1760944510000},"page":"2083-2098","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparing and combining TSPO-PET tracers in tauopathies"],"prefix":"10.1007","volume":"53","author":[{"given":"Harry","family":"Crook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine","family":"Rahmouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes S.","family":"Gn\u00f6rich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim D.","family":"Fryer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young T.","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian N.","family":"Roemer-Cassiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Palleis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Strauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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The following ethics approvals were granted: The research protocol for Cambridge data were approved by the National Research Ethics Service\u2019s East of England Cambridge Central Committee, and the UK Administration of Radioactive Substances Advisory Committee. The study protocol for LMU Munich data was approved by the Ethics Committee of LMU Munich and the Bundesamt f\u00fcr Strahlenschutz (project numbers 17\u2013755 and 17\u2013569).The protocol for the TRIAD study was approved by the Montreal Neurological Institute PET working committee and the Douglas Mental Health University Institute Research Ethics Board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Participants with mental capacity gave their written informed consent to take part in the study. For those who lacked capacity, their participation followed the consultee process in accordance with the law.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"By providing written informed consent to take part in the study, participants consented to anonymised results being published.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The authors have no conflicts of interest to report related to this work. Unrelated to this work, JTO has received honoraria unrelated to this work as DSMB chair or member for TauRx, Axon, Eisai and Novo Nordisk, and has acted as a consultant for Biogen and Roche, and has received research support from Alliance Medical and Merck. JBR is a non-remunerated trustee of the Guarantors of Brain, Darwin College and the PSP Association (UK). He provides consultancy unrelated to the current work to Asceneuron, Astronautx, Astex, Alector, Booster Therapeutics, Curasen, CumulusNeuro, ClinicalInk, Draig Therapeutics, Eisai, Ferrer, Wave, SVHealth, and has research grants from AZ-Medimmune, Janssen, and Lilly as industry partners in the Dementias Platform UK. MM has acted as a consultant for Astex Pharmaceuticals. RP has received honoraria for advisory boards and speaker engagements from Roche, EISAI, Eli Lilly, Biogen, Janssen-Cilag, AstraZeneca, Schwabe, Grifols, Novo Nordisk, and Tabuk, and is a shareholder of Medotrax GmbH and Vistim Ltd. MB received speaker honoraria from GE healthcare, Roche, Iba, and Life Molecular Imaging and is an advisor of GE healthcare, MIAC, and Life Molecular Imaging. NF received speaker or consulting honoraria from GE healthcare, EISAI, Life molecular imaging and MSD.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}