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This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different\n                      <jats:sup>18<\/jats:sup>\n                      F-labeled PSMA ligands to today\u2019s standard radiopharmaceutical\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Differences in background activity among different PSMA-PET tracers lead to variations in tumor-to-background ratios (TBR). In [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DCFPyL-PET, TBR with the liver as the reference organ (TBR\n                      <jats:sub>liver<\/jats:sub>\n                      ) was comparable to [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11-PET, while [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-PSMA-1007-PET and [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-JK-PSMA-7-PET showed significantly lower values. Using the parotid gland as the reference (TBR\n                      <jats:sub>parotidgland<\/jats:sub>\n                      ), [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DCFPyL-PET exhibited significantly higher values, whereas [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-PSMA-1007-PET and [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-JK-PSMA-7-PET were comparable. For the spleen (TBR\n                      <jats:sub>spleen<\/jats:sub>\n                      ), [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-JK-PSMA-7-PET was comparable, but [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DCFPyL-PET and [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-PSMA-1007-PET showed significantly higher and lower values, respectively. An additional Bland-Altman analyses revealed low bias for [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-DCFPyL-PET in TBR\n                      <jats:sub>parotidgland<\/jats:sub>\n                      , whereas significant differences in TBR\n                      <jats:sub>liver<\/jats:sub>\n                      and TBR\n                      <jats:sub>spleen<\/jats:sub>\n                      for the other tracers resulted in higher bias.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Different PSMA-PET tracers exhibit distinct biodistribution patterns, leading to variations in tumor-to-background ratios (TBR) in reference organs such as the liver, parotid gland, and spleen. Patient selection for PSMA-directed radioligand therapy is currently based on a semiquantitative approach using the liver as a reference region in [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11-PET. Thus, the use of alternative [\n                      <jats:sup>18<\/jats:sup>\n                      F]-labeled tracers may result in under- or overestimation of a patient\u2019s suitability for therapy. This highlights the importance of a comprehensive understanding of the differences in tracer-specific uptake behavior for accurate decisions regarding PSMA-expression levels. However, as the patient cohort in this study is at earlier disease stages, the generalizability of these findings to later-stage patients remains unclear and requires further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13550-024-01190-7","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T23:23:05Z","timestamp":1736464985000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0026-824X","authenticated-orcid":false,"given":"Jan","family":"Heilinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin Sabine","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Weis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Weindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Dietlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Krapf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schom\u00e4cker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Neumaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Dietlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Drzezga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Kobe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"1190_CR1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.2967\/jnmt.122.263814","volume":"50","author":"EE Parent","year":"2022","unstructured":"Parent EE, Savir-Baruch B, Gayed IW, Almaguel F, Chin BB, Pantel AR, et al. 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The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All enrolled patients gave written informed consent to participate in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All enrolled patients gave written informed consent for the publication of this study and its accompanying images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A.D. discloses research support from Siemens Healthineers, Life Molecular Imaging, GE Healthcare, AVID Radiopharmaceuticals, SOFIE, Eisai and Novartis\/AAA; Speaker Honorary and\/or Advisory Boards fees from Siemens Healthineers, Sanofi, GE Healthcare, Biogen, Novo Nordisk, Invicro, Novartis\/AAA and Bayer Vital; Stock from Siemens Healthineers, Lantheus Holding; a patent granted for 18\u00a0F-PSMA-JK-7 (PSMA-PET imaging tracer). J.H. discloses Advisory Boards fees from Novartis Pharma GmbH.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}