{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:46:16Z","timestamp":1790412376093,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Approximately 10%\u201320% of prostate cancers progress to metastatic and castration\u2010resistant forms (mCRPC). Radioligand (RLT) therapy with [<jats:sup>177<\/jats:sup>Lu]Lu\u2010prostate\u2010specific membrane antigen (PSMA) is an approved treatment for metastasized mCRPC. Moreover, Actinium\u2010225 (<jats:sup>225<\/jats:sup>Ac), an alpha\u2010emitter isotope, has also been used to label PSMA and, recently, to treat mCRPC patients with encouraging results. However, robust clinical data on [<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA therapy and its comparison with [<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA are still limited. Our aim was to evaluate the role of [<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA in treating mCRPC and compare it with conventional [<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic search was performed in PubMed, Web of Science, Scopus and the Cochrane Register of Controlled Trials from June 2023 to January 2024. This work was conducted in accordance with PRISMA guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After screening and study selection according to PRISMA guidelines, 11 studies were included, 9 of which focused on [<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA only and two on tandem therapy ([<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA\/[<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA). Overall, the pooled proportion of PSA decline in patients was .85 (95% CI: .79\u2013.91, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001); patients pretreated with [<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA achieved a pooled proportion of PSA decline of .90 (95% CI: .82\u2013.97, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). In patients treated with tandem therapy, PSA decline was observed in approximately 90% of them, while PSA response rates above 50% ranged from 53.3% to 65%. Xerostomia was the most frequently reported side effect, along with anaemia, thrombocytopenia and nephrotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, the main results of our study showed that [<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA\u2010617 had a significant therapeutic effect on mCRPC with an acceptable toxicity level. The latter, however, appears greater than with [<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA\u2010617. In future studies, an adequate analysis of the incidence of side effects associated with [<jats:sup>225<\/jats:sup>Ac]Ac\u2010PSMA should be performed to evaluate the role of cumulative toxicity of earlier treatments and the higher frailty of heavily pretreated patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14358","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T10:35:41Z","timestamp":1731926141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["[<sup>225<\/sup>Ac]Ac\u2010PSMA for the treatment of metastatic castration\u2010resistant prostate cancer: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6308-975X","authenticated-orcid":false,"given":"Maria Luisa","family":"Garo","sequence":"first","affiliation":[{"name":"Biostatistic Unit Mathsly Research  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra Petranovi\u0107","family":"Ov\u010dari\u010dek","sequence":"additional","affiliation":[{"name":"Oncology and Nuclear Medicine University Hospital Center Sestre Milosrdnice  Zagreb Croatia"},{"name":"School of Medicine University of Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Fanti","sequence":"additional","affiliation":[{"name":"Nuclear Medicine IRCCS Azienda Ospedaliero\u2010Universitaria S. Orsola  Bologna Italy"},{"name":"Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Giovanella","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, Gruppo Ospedaliero Moncucco, Clinica Moncucco  Lugano Switzerland"},{"name":"Nuclear Medicine University Hospital Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.14740\/wjon1191"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70442-X"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-022-00899-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2016.09.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-020-04934-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.234054"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","unstructured":"MorrisMJ De BonoJS ChiKN et\u00a0al.Phase III study of lutetium\u2010177\u2010PSMA\u2010617 in patients with metastatic castration\u2010resistant prostate cancer (VISION).2021.https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2021.39.15_suppl.LBA4.","DOI":"10.1200\/JCO.2021.39.15_suppl.LBA4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107322"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00529-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.120.251017"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semnuclmed.2008.05.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24137"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-022-08802-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.117.203539"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.11.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijnm.IJNM_130_20"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12149-021-01617-4"},{"issue":"10","key":"e_1_2_9_20_1","first-page":"729","article-title":"Clinical outcomes and molecular profiling of advanced metastatic castration\u2010resistant prostate cancer patients treated with 225Ac\u2010PSMA\u2010617 targeted alpha\u2010radiation therapy","volume":"39","author":"Doelen MJ","year":"2021","journal-title":"Urol Oncol"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-022-05778-w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-023-06340-y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00638-1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-019-04612-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.56211"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.262017"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.18.20845"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.14358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T02:56:28Z","timestamp":1745290588000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.14358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/eci.14358"],"URL":"https:\/\/doi.org\/10.1111\/eci.14358","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,18]]},"assertion":[{"value":"2024-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14358"}}