{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:01:12Z","timestamp":1773993672755,"version":"3.50.1"},"reference-count":219,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007709","name":"Michigan State University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007709","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ovarian cancer (OC) is frequently diagnosed at an advanced stage and characterized by high rates of recurrence despite aggressive cytoreductive surgery and chemotherapy. Relapse is driven by microscopic residual tumors that are disseminated most often throughout the peritoneal cavity, posing significant challenges with conventional systemic therapy. Targeted alpha-particle therapy (TAT) combines molecular targeting with alpha-emitting radionuclides to deliver highly potent and localized cellular damage, uniquely suited for the eradication of small OC tumor clusters within the peritoneal cavity. We conducted an extensive literature search for clinical trials (clinicaltrials.gov) and pre-clinical studies (PubMed, Scopus, Google Scholar) between September 2025 and November 2025. Peer-reviewed articles published in English over the past 20 years that used OC mouse models with reported treatment data were included. Review articles without original data and clinical trials that have been terminated or withdrawn were excluded. In this review, we (1) summarize the biological and physical rationale supporting the use of TAT in OC, (2) discuss the relevant molecular and immunological anti-tumor mechanisms, and (3) critically evaluate early treatment outcomes of 19 pre-clinical and four clinical studies with respect to efficacy, safety, and feasibility. Despite the progress and promising survival outcomes, several challenges remain, including heterogeneous antigen expression, delivery and retention within the peritoneal cavity, off-target toxicity, radiation resistance, radionuclide availability, dosimetry uncertainties, and limitations in clinical trial design. We highlight future directions to overcome these barriers and the continued multidisciplinary efforts essential to translate TAT into effective clinical strategies to treat advanced stages of OC and other solid tumors resistant to conventional treatment. This work was supported with funding available to Kurt R. Zinn as the Hickman Family Endowed Chair in Oncology at Michigan State University.<\/jats:p>","DOI":"10.3390\/molecules31061019","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:12:26Z","timestamp":1773853946000},"page":"1019","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Scoping Review of the Challenges and Future Perspectives in the Use of Alpha-Emitters for Metastatic Ovarian Cancer"],"prefix":"10.3390","volume":"31","author":[{"given":"Lu Lucy","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6937-118X","authenticated-orcid":false,"given":"Satyendra Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelli","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-3397","authenticated-orcid":false,"given":"Jinda","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Radiology, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-4988","authenticated-orcid":false,"given":"Benjamin L.","family":"Viglianti","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7463-4741","authenticated-orcid":false,"given":"Kurt R.","family":"Zinn","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA"},{"name":"College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Radiology, Michigan State University, East Lansing, MI 48824, USA"},{"name":"Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"04155","DOI":"10.7189\/jogh.14.04155","article-title":"Global Burden of Gynaecological Cancers in 2022 and Projections to 2050","volume":"14","author":"Zhu","year":"2024","journal-title":"J. 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