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To evaluate split renal function derived from [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat ([\n                      <jats:sup>18<\/jats:sup>\n                      F]F-rhPSMA-7.3) PET\/CT and to systematically compare its performance with [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 PET\/CT and the reference standard [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3 scintigraphy, we retrospectively analyzed 302 patients with metastatic castration-resistant prostate cancer undergoing PSMA-PET\/CT using either [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009221) or [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200981), along with [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3 scintigraphy, prior to PSMA radioligand therapy. SRF was calculated from PSMA-PET\/CT using mean standardized uptake values and CT-derived renal volumes. SRF was calculated from [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3 using standard integral analysis. SRF derived from PSMA-PET\/CT ([\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat and [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11) was correlated with split renal function obtained from [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3 scintigraphy on a side-specific basis using Pearson correlation and Bland\u2013Altman analysis. Receiver operating characteristic (ROC) analyses were performed to evaluate diagnostic performance for detecting impaired renal function (SRF\u2009\u2264\u200925% and \u2264\u200940%). A PET-based accumulation index (ACI) was explored in relation to estimated glomerular filtration rate (eGFR) in an exploratory, tracer-specific analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Strong correlations were found between PET-SRF and [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3-SRF (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.88 for [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.85 for [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11; both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Bland\u2013Altman analysis showed a smaller mean bias and narrower limits of agreement for [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat (-0.56%; -11.88% to +\u200910.75%) compared with [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11 (-1.18%; -15.3% to +\u200912.95%), with 92% versus 83% of values within \u00b1\u200910%, respectively. ROC analysis confirmed excellent accuracy for identifying [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3-SRF\u2009\u2264\u200925% (area under the curve [AUC]\u2009=\u20090.997 for [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat; AUC\u2009=\u20090.942 for [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11). No significant association was observed between ACI and eGFR for either radiopharmaceutical ([\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat: Spearman\u2019s \u03c1\u2009=\u20090.056,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.414; [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-PSMA-11: Spearman\u2019s \u03c1 = \u2212\u20090.071,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.536).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PSMA-PET\/CT provides reliable estimates of SRF, with [\n                      <jats:sup>18<\/jats:sup>\n                      F]F-flotufolastat showing slightly superior agreement with [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc-MAG3 scintigraphy. This may potentially eliminate the need for additional renal scintigraphy for SRF assessment in the future and may simplify workflows and reduce patient burden.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13550-026-01385-0","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:46:54Z","timestamp":1770144414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estimation of split renal function using [18F]-flotufolastat PET\/CT compared with [68Ga]-PSMA-11 and [99mTc]-MAG3 scintigraphy"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5966-0088","authenticated-orcid":false,"given":"Michael Christian Marius","family":"Gammel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Olufs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Brosch-Lenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Heck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang A.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Eiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Rauscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"1385_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, et al. 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The local ethics committee approved the retrospective analysis (permits: 2019-99_2-S-SR, updated on May 31, 2023).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Isabel Rauscher and Matthias Eiber received consulting fees, research funding and travel support from Blue Earth Diagnostics Ltd.\u00a0Outside the submitted work, Matthias Eiber reports fees from Novartis\/AAA (consultant, speaker), Telix (consultant), Bayer (consultant, research funding), RayzeBio (consultant), Point Biopharma (consultant), Eckert-Ziegler (speaker), ABX GmbH (speaker), and Janssen Pharmaceuticals (consultant, speakers bureau); Parexel (image review) and Bioclinica (image review; and a patent application for rhPSMA. He and other inventors are entitled to royalties on sales of [\n                      18\n                      F]F-flotufolastat.\u00a0Wolfgang A Weber reports research support fees from Blue Earth Diagnostics Ltd, ITM, Novartis, and Pentixapharm. He has also acted as a consultant for these companies.\u00a0There are no other conflicts of interest to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36"}}