{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:43:35Z","timestamp":1792032215148,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      PRRT with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-TATE improves survival in advanced GEP-NETs, but fixed-activity dosing may result in undertreatment or unnecessary toxicity. Individualized dosimetry and tandem-PRRT with\n                      <jats:sup>90<\/jats:sup>\n                      Y\/\n                      <jats:sup>177<\/jats:sup>\n                      Lu have been proposed, but prospective randomized evidence is lacking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      DUONEN is an ongoing multicenter, randomized phase 3 trial (N = 92 planned; 56 analyzed) comparing standard fixed-activity [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-TATE (arm A) with three dosimetry-guided regimens: arm B (\n                      <jats:sup>177<\/jats:sup>\n                      Lu+\n                      <jats:sup>90<\/jats:sup>\n                      Y, variable\n                      <jats:sup>90<\/jats:sup>\n                      Y); arm C (\n                      <jats:sup>177<\/jats:sup>\n                      Lu+\n                      <jats:sup>90<\/jats:sup>\n                      Y, variable\n                      <jats:sup>177<\/jats:sup>\n                      Lu); arm D (variable\n                      <jats:sup>177<\/jats:sup>\n                      Lu). Organ dosimetry was performed after each cycle, with per-cycle activity modifications to respect kidney (23 Gy) and marrow (2 Gy) thresholds. Safety was assessed by laboratory, renal, and hepatic parameters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Activity reductions predominated in arms B and C, while increases were common in arm D. Median cumulative kidney and marrow doses were highest in arm C (29.1 Gy and 0.79 Gy, respectively), driven by\n                      <jats:sup>90<\/jats:sup>\n                      Y contribution. Hematologic declines were observed across all arms, most prominently in lymphocytes and platelets, and correlated with marrow dose but not with categorical dose modifications. Renal function remained stable, and no clinically relevant hepatotoxicity occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This interim analysis demonstrates the feasibility and safety of dosimetry-guided PRRT strategies, including individualized\n                      <jats:sup>177<\/jats:sup>\n                      Lu escalation and tandem\n                      <jats:sup>90<\/jats:sup>\n                      Y\/\n                      <jats:sup>177<\/jats:sup>\n                      Lu. DUONEN provides the first randomized prospective evidence for isotope- and patient-tailored PRRT dosing. Long-term follow-up will clarify their impact on efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=eudract_number:2020-006068-99<\/jats:ext-link>\n                      , identifier 2020-006068-99.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1716247","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:17:01Z","timestamp":1764566221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Dosimetry-guided peptide receptor radionuclide therapy in neuroendocrine tumors: interim safety analysis of the DUONEN 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