{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:37:04Z","timestamp":1792143424278,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>This study aims to retrospectively assess the safety of [225Ac]Ac-PSMA-PRLT, both as monotherapy and in combination (TANDEM) with Lutetium-177, concerning tolerance after the radiopharmaceutical administration and long-term safety, its impact on salivary glands\u2019 function, overall survival (OS), and follow-up duration. Between December 2020 and September 2024, 89 patients received a total of 151 cycles of [225Ac]Ac-PSMA-PRLT. Patients with at least one follow-up (n = 71) were included in the analysis to evaluate xerostomia, as well as long-term hematological, renal, and hepatic toxicities, graded according to CTCAE v5.0. The most common adverse event after the radiopharmaceutical administration was flare pain (n = 16). As of the time of analysis, 68 patients had passed away (76.4%; range of survival 5 days to 39 months, median 7 months), while 21 patients were still alive (23.6%; follow-up duration: 1\u201333 months). Severe (G3\/G4) long-term adverse events were rare, with 15 cases of G3 anemia (21.1%), 6 cases of G3 leukocytopenia (8.4%), and 14 cases of G3\/G4 thrombocytopenia (19.7%). Hematological toxicity was primarily associated with severe bone marrow involvement or prior chemotherapy. Additionally, one case of G3 nephrotoxicity (1.4%) and six cases of G3 hepatotoxicity (8.4%) were observed. Only nine patients (12.7%) reported de novo xerostomia (G1\/G2). In conclusion, this study demonstrates that [225Ac]Ac-PSMA PRLT, both as monotherapy and combined with [177Lu]Lu-PSMA as TANDEM PRLT, is generally safe in terms of both tolerance after the radiopharmaceutical administration and long-term toxicity.<\/jats:p>","DOI":"10.3390\/cancers17030405","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T07:46:29Z","timestamp":1737963989000},"page":"405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long-Term Safety and Survival Outcomes of [225Ac]Ac-PSMA (Prostate-Specific Membrane Antigen) and [225Ac]Ac-\/[177Lu]Lu-PSMA (TANDEM) Radioligand Therapy (PRLT) in Metastatic Castration-Resistant Prostate Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8404-8206","authenticated-orcid":false,"given":"Elisabetta","family":"Perrone","sequence":"first","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"},{"name":"Institute of Nuclear Medicine, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit of Nuclear Medicine, Department of Diagnostic Imaging, Radiation Oncology and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giordano","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lucia","family":"Calcagni","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit of Nuclear Medicine, Department of Diagnostic Imaging, Radiation Oncology and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-2898","authenticated-orcid":false,"given":"Lucia","family":"Leccisotti","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit of Nuclear Medicine, Department of Diagnostic Imaging, Radiation Oncology and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Moretti","sequence":"additional","affiliation":[{"name":"Unit\u00e0 della Fisica per le Scienze della Vita, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-236X","authenticated-orcid":false,"given":"Aleksandr","family":"Eismant","sequence":"additional","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4247-6824","authenticated-orcid":false,"given":"Kriti","family":"Ghai","sequence":"additional","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2285-7783","authenticated-orcid":false,"given":"Tanay","family":"Parkar","sequence":"additional","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Mishra","sequence":"additional","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Heidenreich","sequence":"additional","affiliation":[{"name":"Department of Urology, Uro-Oncology, Robot-Assisted and Reconstructive Surgery, Faculty of Medicine, University of Cologne, University Hospital Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph M.","family":"Wirtz","sequence":"additional","affiliation":[{"name":"Institute of Pathology, St. Elisabeth Hospital K\u00f6ln-Hohenlind, 50935 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-2715","authenticated-orcid":false,"given":"J\u00f6rg","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vivantes Klinikum Spandau, Charit\u00e9\u2013Universit\u00e4tsmedizin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Greifenstein","sequence":"additional","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-0075","authenticated-orcid":false,"given":"Richard P.","family":"Baum","sequence":"additional","affiliation":[{"name":"CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, 65191 Wiesbaden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"ref_1","unstructured":"IARC, and WHO (2024, November 06). 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