{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:07:46Z","timestamp":1784758066155,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"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>[<jats:sup>223<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> and [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> are bone seekers, emitting high LET, and short range (&amp;lt; 100 \u03bcm) alpha-particles. Both radionuclides show similar decay properties; the total alpha energies are comparable (<jats:sup>223<\/jats:sup>Ra: \u224828 MeV, <jats:sup>224<\/jats:sup>Ra: \u224826 MeV). [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> has been used from the mid-1940s until 1990 for treating different bone and joint diseases with activities of up to approximately 50 MBq [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub>. In 2013 [<jats:sup>223<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> obtained marketing authorization by the FDA and by the European Union for the treatment of metastatic prostate cancer with an activity to administer of 0.055 MBq per kg body weight for six cycles. For intravenous injections in humans a model calculation using the biokinetic model of ICRP67 shows a ratio of organ absorbed dose coefficients (<jats:sup>224<\/jats:sup>Ra:<jats:sup>223<\/jats:sup>Ra) between 0.37 (liver) and 0.97 except for the kidneys (2.27) and blood (1.57). For the red marrow as primary organ-at-risk, the ratio is 0.57. The differences are mainly caused be the differing half-lives of the decay products of both radium isotopes. Both radionuclides show comparable DNA damage patterns in peripheral blood mononuclear cells after internal <jats:italic>ex-vivo<\/jats:italic> irradiation. Data on the long-term radiation-associated side effects are only available for treatment with [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub>. Two epidemiological studies followed two patient groups treated with [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> for more than 25 years. One of them was the \u201cSpiess study\u201d, a cohort of 899 juvenile patients who received several injections of [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> with a mean specific activity of 0.66 MBq\/kg. Another patient group of ankylosing spondylitis patients was treated with 10 repeated intravenous injections of [<jats:sup>224<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub>, 1 MBq each, 1 week apart. In total 1,471 of these patients were followed-up in the \u201cWick study\u201d. In both studies, an increased cancer mortality by leukemia and solid cancers was observed. Similar considerations on long-term effects likely apply to [<jats:sup>223<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub> as well since the biokinetics are similar and the absorbed doses in the same range. However, this increased risk will most likely not be observed due to the much shorter life expectancy of prostate cancer patients treated with [<jats:sup>223<\/jats:sup>Ra]RaCl<jats:sub>2<\/jats:sub>.<\/jats:p>","DOI":"10.3389\/fmed.2022.1057373","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T13:56:23Z","timestamp":1672840583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparing absorbed doses and radiation risk of the \u03b1-emitting bone-seekers [223Ra]RaCl2 and [224Ra]RaCl2"],"prefix":"10.3389","volume":"9","author":[{"given":"Michael","family":"Lassmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Eberlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1056\/NEJMoa1213755","article-title":"Alpha emitter radium-223, survival in metastatic prostate cancer","volume":"369","author":"Parker","year":"2013","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s00411-009-0227-y","article-title":"Incidence of leukaemia and other malignant diseases following injections of the short-lived alpha-emitter 224Ra into man","volume":"48","author":"Wick","year":"2009","journal-title":"Radiat Environ Biophys."},{"key":"B3","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1667\/RR1955.1","article-title":"Incidence of malignant diseases in humans injected with radium-224","volume":"174","author":"Nekolla","year":"2010","journal-title":"Radiat Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00393-005-0009-0","article-title":"Effectiveness and safety of radium chloride in the treatment of ankylosing spondylitis. Results of an observational study","volume":"65","author":"Alberding","year":"2006","journal-title":"Z Rheumatol."},{"key":"B5","first-page":"A106","article-title":"Die Behandlung osteoblastischer Metastasen mit Radium-224-Chlorid","volume":"47","author":"Groth","year":"2008","journal-title":"Nuklearmedizin."},{"key":"B6","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13550-018-0422-4","article-title":"Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with 224Ra","volume":"8","author":"Schumann","year":"2018","journal-title":"EJNMMI Res."},{"key":"B7","author":"Eckerman","year":"2008","journal-title":"MIRD: Radionuclide Data and Decay Schemes"},{"key":"B8","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s00411-002-0164-5","article-title":"Therapy of ankylosing spondylitis with 224Ra-radium chloride: dosimetry and risk considerations","volume":"41","author":"Lassmann","year":"2002","journal-title":"Radiat Environ Biophys."},{"key":"B9","year":"","journal-title":"Publication 67: Age-dependent doses to members of the public from intake of radionuclides: Part 2 Ingestion dose coefficients."},{"key":"B10","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00259-012-2265-y","article-title":"Dosimetry of 223Ra-chloride: dose to normal organs and tissues","volume":"40","author":"Lassmann","year":"2013","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1007\/s00259-013-2427-6","article-title":"Phase I pharmacokinetic and biodistribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer","volume":"40","author":"Carrasquillo","year":"2013","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.2967\/jnumed.115.157123","article-title":"A Phase 1, open-label study of the biodistribution, pharmacokinetics, and dosimetry of 223Ra-Dichloride in patients with hormone-refractory prostate cancer and skeletal metastases","volume":"56","author":"Chittenden","year":"2015","journal-title":"J Nucl Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s12149-016-1093-8","article-title":"Pharmacokinetics of single dose radium-223 dichloride (BAY 88-8223) in Japanese patients with castration-resistant prostate cancer and bone metastases","volume":"30","author":"Yoshida","year":"2016","journal-title":"Ann Nucl Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1007\/s00259-020-05170-6","article-title":"alpha-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients","volume":"48","author":"Schumann","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B15","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00259-015-3150-2","article-title":"Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223Ra-dichloride","volume":"43","author":"Pacilio","year":"2016","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B16","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s40658-021-00388-1","article-title":"Radiopharmacokinetic modelling and radiation dose assessment of (223)Ra used for treatment of metastatic castration-resistant prostate cancer","volume":"8","author":"H\u00f6llriegl","year":"2021","journal-title":"EJNMMI Phys."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/0146645317734963","article-title":"ICRP Publication 137: Occupational Intakes of Radionuclides: Part 3","volume":"46","author":"Paquet","year":"2017","journal-title":"Ann ICRP."},{"key":"B18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00411-005-0275-x","article-title":"Chromosomal aberrations in peripheral lymphocytes of patients treated with radium-224 for ankylosing spondylitis","volume":"44","author":"Stephan","year":"2005","journal-title":"Radiat Environ Biophys."},{"key":"B19","doi-asserted-by":"publisher","first-page":"210","DOI":"10.2307\/3575876","article-title":"Radium retention in mature beagles injected at 5 years of age","volume":"94","author":"Lloyd","year":"1983","journal-title":"Radiat Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"110159","DOI":"10.1016\/j.apradiso.2022.110159","article-title":"Catalogue of dose rate constants for more than 400 radionuclides in terms of ambient dose H(*) and comparison of figures to ambient dose equivalent H(*)(10)","volume":"184","author":"Stettner","year":"2022","journal-title":"Appl Radiat Isot."},{"key":"B21","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1097\/HP.0b013e3182a82b37","article-title":"Radiation safety considerations for the use of [223Ra]RaCl2 DE in men with castration-resistant prostate cancer","volume":"106","author":"Dauer","year":"2014","journal-title":"Health Phys."},{"key":"B22","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.2307\/3580102","article-title":"Malignancies in patients treated with high doses of radium-224","volume":"152","author":"Nekolla","year":"1999","journal-title":"Radiat Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1667\/0033-7587(","article-title":"Induction of malignant bone tumors in radium-224 patients: risk estimates based on the improved dosimetry","volume":"153","author":"Nekolla","year":"2000","journal-title":"Radiat Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e919","DOI":"10.1016\/j.clgc.2018.03.007","article-title":"Hematologic Toxicity From Radium-223 Therapy for Bone Metastases in Castration-Resistant Prostate Cancer: Risk Factors and Practical Considerations","volume":"16","author":"Jacene","year":"2018","journal-title":"Clin Genitourin Cancer."},{"key":"B25","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1097\/MNM.0b013e328353bb6e","article-title":"Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases","volume":"33","author":"Hindorf","year":"2012","journal-title":"Nucl Med Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/j.ejmp.2016.09.013","article-title":"The Italian multicentre dosimetric study for lesion dosimetry in 223Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria","volume":"32","author":"Pacilio","year":"2016","journal-title":"Phys Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s40658-022-00481-z","article-title":"Quantitative SPECT\/CT imaging of lead-212: a phantom study","volume":"9","author":"Kvassheim","year":"2022","journal-title":"EJNMMI Phys."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.2967\/jnumed.121.263230","article-title":"Targeted alpha-emitter therapy with 212Pb-DOTAMTATE for the treatment of metastatic SSTR-expressing neuroendocrine tumors: first-in-humans dose-escalation clinical trial","volume":"63","author":"Delpassand","year":"2022","journal-title":"J Nucl Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"280","DOI":"10.2307\/3576005","article-title":"Radium-224 retention, distribution, and dosimetry in beagles","volume":"92","author":"Lloyd","year":"1982","journal-title":"Radiat Res."},{"key":"B30","first-page":"234","article-title":"Storage and excretion of Radium 224 (-thorium X) during treatment of ankylosing spondylitis","volume":"29","author":"Klemm","year":"1970","journal-title":"Z Rheumaforsch."},{"key":"B31","doi-asserted-by":"publisher","first-page":"5025","DOI":"10.1088\/0031-9155\/52\/16\/021","article-title":"Treatment of solid tumors by interstitial release of recoiling short-lived alpha emitters","volume":"52","author":"Arazi","year":"2007","journal-title":"Phys Med Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"015015","DOI":"10.1088\/1361-6560\/ab5b73","article-title":"Diffusing alpha-emitters radiation therapy: approximate modeling of the macroscopic alpha particle dose of a point source","volume":"65","author":"Arazi","year":"2020","journal-title":"Phys Med Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0248133","DOI":"10.1371\/journal.pone.0248133","article-title":"Radon-220 diffusion from 224Ra-labeled calcium carbonate microparticles: Some implications for radiotherapeutic use","volume":"16","author":"Napoli","year":"2021","journal-title":"PLoS ONE."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1038\/s41598-018-20364-7","article-title":"DNA damage in leukocytes after internal ex-vivo irradiation of blood with the alpha-emitter 223Ra","volume":"8","author":"Schumann","year":"2018","journal-title":"Sci Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3981","DOI":"10.1007\/s00259-022-05860-3","article-title":"Repair of alpha-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with 223Ra","volume":"49","author":"G\u00f6ring","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e0232597","DOI":"10.1371\/journal.pone.0232597","article-title":"Administration of lower doses of radium-224 to ankylosing spondylitis patients results in no evidence of significant overall detriment","volume":"15","author":"Priest","year":"2020","journal-title":"PLoS ONE."},{"key":"B37","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/00004032-198306001-00001","article-title":"Dose-response relationships for radium-induced bone sarcomas","volume":"44","author":"Rowland","year":"1983","journal-title":"Health Phys."},{"key":"B38","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/oxfordjournals.rpd.a006265","article-title":"Target cells in internal dosimetry","volume":"105","author":"Gossner","year":"2003","journal-title":"Radiat Prot Dosimetry."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1057373\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T23:02:09Z","timestamp":1672873329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1057373\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":38,"alternative-id":["10.3389\/fmed.2022.1057373"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.1057373","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]},"article-number":"1057373"}}