{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:43:15Z","timestamp":1790095395605,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Peptide receptor radionuclide therapy (PRRT) using radiopharmaceuticals labelled with Lutetium-177 is currently a therapeutic option for patients with advanced neuroendocrine neoplasms overexpressing somatostatin receptors (SSTRs). One promising option that has gained interest for PRRT is using alpha-emitting radioisotopes such as Actinium-225. The aim of this study was to perform a systematic review and meta-analysis on the efficacy and safety of radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms. Materials and Methods: A comprehensive literature search of studies on radioligand therapy with Actinium-225 DOTATATE in neuroendocrine neoplasms was carried out. Three different bibliographic databases (Cochrane Library, Embase, and PubMed\/MEDLINE) were screened up to May 2025. Eligible articles were selected, relevant data were extracted, and the main findings on efficacy and safety are summarized through a systematic review. Furthermore, proportional meta-analyses on the disease response rate and disease control rate were performed. Results: Five studies (153 patients) published from 2020 were included in the systematic review. The pooled disease response rate and disease control rate of radioligand therapy using Actinium-225 DOTATATE were 51.6% and 88%, respectively. This treatment was well-tolerated in most patients with advanced, metastatic or inoperable neuroendocrine neoplasms. Conclusions: Radioligand therapy with Actinium-225 DOTATATE in advanced, metastatic or inoperable neuroendocrine neoplasms is effective with an acceptable toxicity profile and potential advantages compared with SSTR-ligands labelled with Lutetium-177. Currently, the number of published studies on this treatment is still limited, and results from multicenter randomized controlled trials are needed to translate this therapeutic option into clinical practice.<\/jats:p>","DOI":"10.3390\/medicina61081341","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:19:22Z","timestamp":1753370362000},"page":"1341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy and Safety of Radioligand Therapy with Actinium-225 DOTATATE in Patients with Advanced, Metastatic or Inoperable Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5438-8230","authenticated-orcid":false,"given":"Alessio","family":"Rizzo","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Candiolo Cancer Institute, FPO-IRCCS, 10060 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Imperiale","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, University Hospitals of Strasbourg, University of Strasbourg, 67200 Strasbourg, France"},{"name":"Nuclear Medicine and Molecular Imaging, ICANS, 67200 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8071-6513","authenticated-orcid":false,"given":"Roberto C.","family":"Delgado Bolton","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, University Hospital San Pedro and Centre for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"},{"name":"Servicio C\u00e1ntabro de Salud, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0810-6494","authenticated-orcid":false,"given":"Domenico","family":"Albano","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, ASST Spedali Civili di Brescia and University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3932-1330","authenticated-orcid":false,"given":"Francesco","family":"Fiz","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ente Ospedaliero Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-1471","authenticated-orcid":false,"given":"Arnoldo","family":"Piccardo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ente Ospedaliero Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8214-562X","authenticated-orcid":false,"given":"Marco","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-5364","authenticated-orcid":false,"given":"Gaetano","family":"Paone","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera italiana, 6900 Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-780X","authenticated-orcid":false,"given":"Giorgio","family":"Treglia","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland"},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera italiana, 6900 Lugano, Switzerland"},{"name":"Faculty of Biology and Medicine, University of Lausanne, 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.6004\/jnccn.2021.0032","article-title":"Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology","volume":"19","author":"Shah","year":"2021","journal-title":"J. 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