{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:59:06Z","timestamp":1788998346700,"version":"build-2803163510"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"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>Metastases are the primary cause of death among cancer patients and efficacious new treatments are sorely needed. Targeted alpha-emitting radiopharmaceuticals that are highly cytotoxic may fulfill this critical need. The focus of this paper is to describe and explore a novel technology that may improve the therapeutic effect of targeted alpha therapy by combining two radionuclides from the same decay chain in the same solution. We hypothesize that the dual targeting solution containing bone-seeking <jats:sup>224<\/jats:sup>Ra and cell-directed complexes of progeny <jats:sup>212<\/jats:sup>Pb is a promising approach to treat metastatic cancers with bone and soft tissue lesions as well as skeletal metastases of mixed lytic\/osteoblastic nature. A novel liquid <jats:sup>224<\/jats:sup>Ra\/<jats:sup>212<\/jats:sup>Pb-generator for rapid preparation of a dual targeting solution is described. Cancer cell targeting monoclonal antibodies, their fragments, synthetic proteins or peptides can all be radiolabeled with <jats:sup>212<\/jats:sup>Pb in the <jats:sup>224<\/jats:sup>Ra-solution in transient equilibrium with daughter nuclides. Thus, <jats:sup>224<\/jats:sup>Ra targets stromal elements in sclerotic bone metastases and <jats:sup>212<\/jats:sup>Pb-chelated-conjugate targets tumor cells of metastatic prostate cancer or osteosarcoma. The dual targeting solution may also be explored to treat metastatic breast cancer or multiple myeloma after manipulation of bone metastases to a more osteoblastic phenotype by the use of bisphosphonates, denosumab, bortezomib or hormone therapy prior to treatment. This may improve targeting of bone-seeking <jats:sup>224<\/jats:sup>Ra and render an augmented radiation dose deposited within metastases. Our preliminary preclinical studies provide conceptual evidence that the dual <jats:sup>224<\/jats:sup>Ra-solution with bone or tumor-targeted delivery of <jats:sup>212<\/jats:sup>Pb has potential to inhibit cancer metastases without significant toxicity. In some settings, the use of a booster dose of purified <jats:sup>212<\/jats:sup>Pb-conjugate alone could be required to elevate the effect of this tumor cell directed component, if needed, e.g., in a fractionated treatment regimen, where the dual targeting solution will act as maintenance treatment.<\/jats:p>","DOI":"10.3389\/fmed.2022.1051825","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T05:17:25Z","timestamp":1673932645000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Dual targeting with 224Ra\/212Pb-conjugates for targeted alpha therapy of disseminated cancers: A conceptual approach"],"prefix":"10.3389","volume":"9","author":[{"given":"Asta","family":"Juzeniene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilde 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