{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:36:59Z","timestamp":1792442219810,"version":"4.5.0"},"reference-count":103,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"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>Radioligand therapy (RLT) is a targeted treatment modality that combines a tumour-specific ligand with a therapeutic radionuclide. Once administered, the radiopharmaceutical binds selectively to cancer-associated targets, delivering cytotoxic radiation directly to tumour cells while sparing surrounding tissues. Two RLT agents, [177Lu]Lu-DOTA-TATE (Lutathera\u00ae) and [177Lu]Lu-PSMA-617 (Pluvicto\u00ae), have received regulatory approval for the treatment of advanced gastroenteropancreatic neuroendocrine tumours and metastatic castration-resistant prostate cancer, respectively. As of July 2025, more than 400 clinical trials are registered, exploring novel molecular targets such as FAP, CAIX, and GRPR, as well as alternative radionuclides and combination regimens in both solid and haematologic malignancies. In this review, we describe the design principles and mechanisms of action of RLT, summarise clinical evidence for approved and emerging radiopharmaceuticals, and discuss current global disparities in access and availability. Finally, we outline the main clinical challenges, including fixed dosing regimens, resistance, toxicity, and variability in patient selection and response assessment. Continued research to optimise radiopharmaceutical design, together with investment in infrastructure, workforce capacity, and international collaboration, will be essential to expand access and realise the full potential of RLT as a leading treatment strategy in modern oncology.<\/jats:p>","DOI":"10.3390\/cancers17213412","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:35:11Z","timestamp":1761269711000},"page":"3412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Radioligand Therapy in Cancer Management: A Global Perspective"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8207-1256","authenticated-orcid":false,"given":"Gaia","family":"Ninatti","sequence":"first","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, VIC 3084, Australia"},{"name":"Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia"},{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8641-456X","authenticated-orcid":false,"given":"Sze Ting","family":"Lee","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, VIC 3084, Australia"},{"name":"Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Bundoora, Melbourne, VIC 3086, Australia"},{"name":"School of Health and Biomedicine, RMIT University, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-295X","authenticated-orcid":false,"given":"Andrew M.","family":"Scott","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, VIC 3084, Australia"},{"name":"Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Melbourne, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Bundoora, Melbourne, VIC 3086, Australia"},{"name":"Faculty of Medicine, University of Melbourne, Parkville, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.3747\/co.27.5223","article-title":"A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future","volume":"27","author":"Esfahani","year":"2020","journal-title":"Curr. 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