{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:08:19Z","timestamp":1773194899436,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with Lutetium-177 (\n                      <jats:sup>177<\/jats:sup>\n                      Lu) and Actinium-225 (\n                      <jats:sup>225<\/jats:sup>\n                      Ac) is increasingly used in metastatic castration-resistant prostate cancer (mCRPC), but head-to-head prospective data remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted an observational study of mCRPC patients treated with\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA (n=116; 2022\u20132023) or\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA (n=43; 2023). Primary outcomes were PSA response (\u226550% decline) and overall survival (OS); secondary outcomes included hematologic toxicity. Treatments were given every 8 \u00b1 2 weeks (1\u20136 cycles; median 2) with administered activity typically 5\u201310 GBq (median 7.5 GBq) alongside standard androgen-deprivation therapy; concurrent chemotherapy was not allowed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median follow-up was 9 months (\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA) and 10 months (\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA). Median OS was 13.0 months (95% CI 9.5\u201318.3) for\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA and 11.8 months (95% CI 7.0\u2013NR) for\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA, with no significant difference between groups. A \u226550% PSA decline occurred in 42.2% (\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA) and 40.5% (\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA). Receiving &amp;gt;2 RLT courses was associated with longer OS in both cohorts (\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA: 18.3 vs 7.3 months;\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA: OS not reached vs 5.2 months). Trends toward worse outcomes were observed in patients with visceral (especially hepatic) metastases and in those previously exposed to taxanes. Hematologic toxicity was frequent but mostly grade 1\u20132: anemia 66% (\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA) vs 58% (\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA), leukopenia 59% vs 57%, thrombocytopenia 47% vs 48%; treatment-related deaths were not observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this observational experience,\n                      <jats:sup>225<\/jats:sup>\n                      Ac-PSMA and\n                      <jats:sup>177<\/jats:sup>\n                      Lu-PSMA achieved comparable survival and PSA response with predominantly mild-to-moderate hematologic toxicity. Greater treatment exposure (&amp;gt;2 cycles) correlated with improved survival. Randomized trials are warranted to refine sequencing and patient selection for PSMA-RLT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1744007","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:29:36Z","timestamp":1773120576000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Actinium-225-PSMA versus lutetium-177-PSMA radioligand therapy for metastatic castration-resistant prostate cancer: results of an observational study"],"prefix":"10.3389","volume":"16","author":[{"given":"Tatiana Yu","family":"Kochetova","sequence":"first","affiliation":[{"name":"National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation","place":["Obninsk, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail B.","family":"Potievskiy","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation","place":["Obninsk, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia A.","family":"Nekrasova","sequence":"additional","affiliation":[{"name":"Department of Oncourology, Moscow City Oncological Hospital \u2116. 62","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy V.","family":"Krylov","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation","place":["Obninsk, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter V.","family":"Shegai","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation","place":["Obninsk, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei A.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation","place":["Obninsk, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei D.","family":"Kaprin","sequence":"additional","affiliation":[{"name":"National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation","place":["Obninsk, Russia"]},{"name":"Department of Urology and Operative Nephrology, Peoples\u2019 Friendship University of Russia (RUDN University)","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/eci.14358","article-title":"225Ac]Ac-PSMA for the treatment of metastatic castration-resistant prostate cancer: A systematic review and meta-analysis","volume":"54","author":"Garo","year":"2024","journal-title":"Eur J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.123.265414","article-title":"177Lu-PSMA-Radioligand Therapy Efficacy Outcomes in Taxane-Na\u00efve Versus Taxane-Treated Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Metaanalysis","volume":"64","author":"Satapathy","year":"2023","journal-title":"J Nucl Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.219543","article-title":"Clinical Outcomes of 177Lu-PSMA Radioligand Therapy in Earlier and Later Phases of Metastatic Castration-Resistant Prostate Cancer Grouped by Previous Taxane Chemotherapy","volume":"60","author":"Barber","year":"2019","journal-title":"J Nucl Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263045","article-title":"mCRPC Patients Receiving 225Ac-PSMA-617 Therapy in the Post-Androgen Deprivation Therapy Setting: Response to Treatment and Survival Analysis","volume":"63","author":"Sathekge","year":"2022","journal-title":"J Nucl Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.euros.2024.06.010","article-title":"Contemporary Treatment Patterns and Oncological Outcomes of Metastatic Hormone-sensitive Prostate Cancer and First- to Sixth- line Metastatic Castration-resistant Prostate Cancer Patients","volume":"66","author":"Wenzel","year":"2024","journal-title":"Eur Urol Open Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.eururo.2021.03.004","article-title":"A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177-labeled Prostate-specific Membrane Antigen-targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer","volume":"80","author":"Sadaghiani","year":"2021","journal-title":"Eur Urol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24857","article-title":"The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 Prostate-Specific Membrane Antigen, in Patients With Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis","volume":"85","author":"Besiroglu","year":"2025","journal-title":"Prostate"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.06.011","article-title":"Prostate cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Parker","year":"2020","journal-title":"Ann Oncol"},{"key":"B11","volume-title":"Prostate cancer (version 3.2024)","year":"2024"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.120.251017","article-title":"First clinical results for PSMA-targeted alpha-therapy using 225Ac-PSMA-I&T in advanced-mCRPC patients","volume":"62","author":"Zacherl","year":"2021","journal-title":"J Nucl Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2022.07.001","article-title":"Validation of prognostic and predictive models for therapeutic response in patients treated with 177Lu-PSMA versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a post hoc analysis from a randomised, open-label, phase 2 trial","volume":"6","author":"Gafita","year":"2023","journal-title":"Eur Urol Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263274","article-title":"The VISION forward: recognition and implication of PSMA-\/18F-FDG+ mCRPC","volume":"63","author":"Jadvar","year":"2022","journal-title":"J Nucl Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-022-05882-x","article-title":"Measuring response in metastatic castration-resistant prostate cancer using PSMA PET\/CT: comparison of RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 criteria","volume":"49","author":"Gafita","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-3-1-81","article-title":"Prostate-specific membrane antigen expression in normal and malignant human tissues","volume":"3","author":"Silver","year":"1997","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2018.2494","article-title":"Actinium-225 for Targeted \u03b1 Therapy: Coordination Chemistry and Current Chelation Approaches","volume":"33","author":"Thiele","year":"2018","journal-title":"Cancer Biother Radiopharm"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30198-0","article-title":"177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study","volume":"19","author":"Hofman","year":"2018","journal-title":"Lancet Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.234567","article-title":"Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of 177Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer","volume":"61","author":"Violet","year":"2020","journal-title":"J Nucl Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S1470-2045(23)00529-6","article-title":"Overall survival with 177Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial","volume":"25","author":"Hofman","year":"2024","journal-title":"Lancet Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.eururo.2024.09.020","article-title":"A Meta-Analysis and Meta-Regression of the Efficacy, Toxicity, and Quality of Life Outcomes Following Prostate-Specific Membrane Antigen Radioligand Therapy Utilising Lutetium-177 and Actinium-225 in Metastatic Prostate Cancer","volume":"87","author":"Yang","year":"2025","journal-title":"Eur Urol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1159\/000531246","article-title":"Efficacy and safety of actinium-225 prostate-specific membrane antigen radioligand therapy in metastatic prostate cancer: a systematic review and metanalysis","volume":"32","author":"Parida","year":"2023","journal-title":"Med Princ Pract"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.796657","article-title":"Efficacy and safety of 225AcPSMA-617-targeted alpha therapy in metastatic castrationresistant prostate cancer: a systematic review and meta-analysis","volume":"12","author":"Ma","year":"2022","journal-title":"Front Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.11.013","article-title":"Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA","volume":"79","author":"Feuerecker","year":"2021","journal-title":"Eur Urol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24598","article-title":"Response to RL-225Ac in prostate cancer: Effect of prior treatment with RL-177Lu: A systematic review of the literature","volume":"83","author":"Stangl-Kremser","year":"2023","journal-title":"Prostate"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000005583","article-title":"Outcome and Renal Safety of PSMA-Targeted Radioligand Therapy in mCRPC Patients With Preexisting Impaired Renal Function","volume":"50","author":"Bastian","year":"2025","journal-title":"Clin Nucl Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01234-5","article-title":"177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial","volume":"404","author":"Morris","year":"2024","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.123.266123","article-title":"177Lu-PSMA-617 Versus Docetaxel in Chemotherapy-Na\u00efve Metastatic Castration-Resistant Prostate Cancer: Final Survival Analysis of a Phase 2 Randomized, Controlled Trial","volume":"64","author":"Satapathy","year":"2023","journal-title":"J Nucl Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s00259-017-3891-0","article-title":"Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review","volume":"45","author":"von Eyben","year":"2018","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.123.265999","article-title":"177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer and Prior 223Ra (RALU Study)","volume":"64","author":"Rahbar","year":"2023","journal-title":"J Nucl Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-018-4146-3","article-title":"225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study","volume":"46","author":"Sathekge","year":"2019","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00638-1","article-title":"Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study","volume":"25","author":"Sathekge","year":"2024","journal-title":"Lancet Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"102260","DOI":"10.1016\/j.clgc.2024.102260","article-title":"Safety and Efficacy of 177Lu-PSMA Therapy Following 223Radium Treatment: A Retrospective Multinational Real-World Analysis","volume":"23","author":"Giannini","year":"2025","journal-title":"Clin Genitourin Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1744007\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:29:37Z","timestamp":1773120577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1744007\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":33,"alternative-id":["10.3389\/fonc.2026.1744007"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1744007","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"article-number":"1744007"}}