{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:05:10Z","timestamp":1791461110488,"version":"4.3.4"},"reference-count":174,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Bone radiopharmaceuticals have evolved from early palliative agents into integral components of targeted precision oncology and theranostics. This review comprehensively traces the historical trajectory, pathophysiological mechanisms, and clinical applications of bone-directed nuclear medicine. We contrast primary bone malignancies\u2014which directly produce malignant osteoid matrix\u2014with metastatic bone disease, which colonizes the endosteal niche via the RANK\/RANKL\/OPG axis and the metastatic vicious cycle. The molecular mechanisms governing skeletal radioisotope localization are systematically detailed, encompassing calcium mimetics (223Ra), inorganic phosphate integration (32P), hydroxyapatite chemisorption (99mTc-labeled diphosphonates), isomorphous surface exchange ([18F]NaF), and direct biomarker targeting. Furthermore, we highlight the therapeutic transition from medium-range beta-emitters to high-linear energy transfer (LET) targeted alpha therapy (225Ac), nanometer-scale Auger electron emitters, and cell-directed theranostic vectors. By unifying radiopharmaceutical chemistry, microdosimetry, and emerging artificial intelligence-driven personalized dosimetry, this review provides a strategic roadmap for advancing precision bone endoradiotherapy.<\/jats:p>","DOI":"10.3390\/biology15191784","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:26:53Z","timestamp":1791458813000},"page":"1784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bone Radiopharmaceuticals: Evolution from Palliative Therapy to Targeted Precision Oncology and Theranostics"],"prefix":"10.3390","volume":"15","author":[{"given":"Andras","family":"Polyak","sequence":"first","affiliation":[{"name":"Radiation Therapy and Radiation Oncology, Medical School OWL (East Westphalia-Lippe), Bielefeld University, Morgenbreede 1, D-33615 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Matuschek","sequence":"additional","affiliation":[{"name":"Radiation Therapy and Radiation Oncology, Medical School OWL (East Westphalia-Lippe), Bielefeld University, Morgenbreede 1, D-33615 Bielefeld, Germany"},{"name":"Department of Radiation Oncology, Klinikum Bielefeld Mitte, Medical School and University Medical Center East Westphalia-Lippe, Bielefeld University, Teutoburger Str 50, D-33604 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6243s","DOI":"10.1158\/1078-0432.CCR-06-0931","article-title":"Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity","volume":"12","author":"Coleman","year":"2006","journal-title":"Clin. 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