{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:42Z","timestamp":1792088022687,"version":"4.4.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Targeted alpha therapy (TAT) is a promising approach for addressing unmet needs in oncology. Inherent properties make \u03b1-emitting radionuclides well suited to cancer therapy, including high linear energy transfer (LET), penetration range of 2\u201310 cell layers, induction of complex double-stranded DNA breaks, and immune-stimulatory effects. Several alpha radionuclides, including radium-223 (<jats:sup>223<\/jats:sup>Ra), actinium-225 (<jats:sup>225<\/jats:sup>Ac), and thorium-227 (<jats:sup>227<\/jats:sup>Th), have been investigated. Conjugation of tumor targeting modalities, such as antibodies and small molecules, with a chelator moiety and subsequent radiolabeling with \u03b1-emitters enables specific delivery of cytotoxic payloads to different tumor types. <jats:sup>223<\/jats:sup>Ra dichloride, approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with bone-metastatic disease and no visceral metastasis, is the only approved and commercialized alpha therapy. However, <jats:sup>223<\/jats:sup>Ra dichloride cannot currently be complexed to targeting moieties. In contrast to <jats:sup>223<\/jats:sup>Ra, <jats:sup>227<\/jats:sup>Th may be readily chelated, which allows radiolabeling of tumor targeting moieties to produce targeted thorium conjugates (TTCs), facilitating delivery to a broad range of tumors. TTCs have shown promise in pre-clinical studies across a range of tumor-cell expressing antigens. A clinical study in hematological malignancy targeting CD22 has demonstrated early signs of activity. Furthermore, pre-clinical studies show additive or synergistic effects when TTCs are combined with established anti-cancer therapies, for example androgen receptor inhibitors (ARI), DNA damage response inhibitors such as poly (ADP)-ribose polymerase inhibitors or ataxia telangiectasia and Rad3-related kinase inhibitors, as well as immune checkpoint inhibitors.<\/jats:p>","DOI":"10.3389\/fmed.2022.1071086","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T09:47:46Z","timestamp":1673257666000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Targeted thorium-227 conjugates as treatment options in oncology"],"prefix":"10.3389","volume":"9","author":[{"given":"Jenny","family":"Karlsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph 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