{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:47:51Z","timestamp":1791668871082,"version":"4.3.4"},"reference-count":118,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This review outlines the accomplishments and potential developments of targeted alpha (\u03b1) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of \u03b1-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common \u03b1-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of \u03b1-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinical trials; and an outlook on the future of TAT.<\/jats:p>","DOI":"10.3390\/pharmaceutics13010049","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T14:31:49Z","timestamp":1609425109000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":184,"title":["Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications"],"prefix":"10.3390","volume":"13","author":[{"given":"Bryce J. B.","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Oncology, University of Alberta, 11560 University Ave, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan D.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, 11560 University Ave, Edmonton, AB T6G 1Z2, Canada"},{"name":"Edmonton Radiopharmaceutical Center, Alberta Health Services, 11560 University Ave, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Wuest","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Alberta, 11560 University Ave, Edmonton, AB T6G 1Z2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"878","DOI":"10.2967\/jnumed.116.186338","article-title":"\u03b1-Emitters for radiotherapy: From basic radiochemistry to clinical studies\u2014Part 1","volume":"59","author":"Poty","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1631\/jzus.B1400131","article-title":"Therapeutic radionuclides in nuclear medicine: Current and future prospects","volume":"15","author":"Yeong","year":"2014","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.2967\/jnumed.117.204651","article-title":"\u03b1-Emitters for radiotherapy: From basic radiochemistry to clinical studies\u2014Part 2","volume":"59","author":"Poty","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12210-020-00900-2","article-title":"The five \u201cW\u201ds and \u201cHow\u201d of targeted alpha therapy: Why? Who? What? Where? When? and How?","volume":"31","author":"Sollini","year":"2020","journal-title":"Rend. Fis. Acc. Lincei"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41181-019-0075-2","article-title":"Auger electrons for cancer therapy\u2014A review","volume":"4","author":"Ku","year":"2019","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3389\/fonc.2013.00324","article-title":"The potential and hurdles of targeted alpha therapy\u2014Clinical trials and beyond","volume":"3","author":"Elgqvist","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/jmrs.227","article-title":"Lutetium177PSMA radionuclide therapy for men with prostate cancer: A review of the current literature and discussion of practical aspects of therapy","volume":"64","author":"Emmett","year":"2017","journal-title":"J. Med. Radiat. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1080\/17474124.2019.1685381","article-title":"177Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors","volume":"13","author":"Das","year":"2019","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/rpd\/ncq385","article-title":"Molecular and cellular radiobiological effects of Auger emitting radionuclides","volume":"143","author":"Kassis","year":"2010","journal-title":"Radiat. Prot. Dosim."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1007\/s00259-005-1877-x","article-title":"111In-labelled somatostatin analogues in a rat tumour model: Somatostatin receptor status and effects of peptide receptor radionuclide therapy","volume":"32","author":"Capello","year":"2005","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3171\/2010.2.JNS091211","article-title":"A phase II study of anti\u2013epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme","volume":"113","author":"Li","year":"2010","journal-title":"J. Neurosurg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/bjc.1998.61","article-title":"Differential cytotoxicity of [123I]IUdR, [125I]IUdR and [131I]IUdR to human glioma cells in monolayer or spheroid culture: Effect of proliferative heterogeneity and radiation cross-fire","volume":"77","author":"Mairs","year":"1998","journal-title":"Br. J Cancer"},{"key":"ref_13","first-page":"75","article-title":"Nonuniformity of tumor dose in radioimmunotherapy","volume":"31","author":"Humm","year":"1990","journal-title":"J. Nucl. Med."},{"key":"ref_14","first-page":"166","article-title":"Alpha-emitting bismuth cyclohexylbenzyl DTPA constructs of recombinant humanized anti-CD33 antibodies: Pharmacokinetics, bioactivity, toxicity and chemistry","volume":"40","author":"Nikula","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_15","first-page":"1881","article-title":"Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb-trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice","volume":"40","author":"Dong","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.2967\/jnumed.116.178673","article-title":"225Ac-PSMA-617 for PSMA-targeted \u03b1-radiation therapy of metastatic castration-resistant prostate cancer","volume":"57","author":"Kratochwil","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13550-016-0240-5","article-title":"Improved safety and efficacy of 213Bi-DOTATATE-targeted alpha therapy of somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with l-lysine","volume":"6","author":"Chan","year":"2016","journal-title":"EJNMMI Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chan, H.S., de Blois, E., Morgenstern, A., Bruchertseifer, F., de Jong, M., Breeman, W., and Konijnenberg, M. (2017). In vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181473"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kozempel, J., Mokhodoeva, O., and Vlk, M. (2018). Progress in targeted alpha-particle therapy. What we learned about recoils release from in vivo generators. Molecules, 23.","DOI":"10.3390\/molecules23030581"},{"key":"ref_20","unstructured":"Sonzogni, A., and Shu, B. (2020, September 08). Nudat 2.8 (Nuclear Structure and Decay Data), Available online: Nndc.bnl.gov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"306","DOI":"10.2174\/1874471011104040306","article-title":"Actinium-225 in targeted alpha-particle therapeutic applications","volume":"4","author":"Scheinberg","year":"2011","journal-title":"Curr. Radiopharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.apradiso.2016.10.009","article-title":"Cherenkov light production from the \u03b1-emitting decay chains of 223Ra, 212Pb, and 149Tb for cherenkov luminescence imaging","volume":"118","author":"Wood","year":"2016","journal-title":"Appl. Radiat. Isot."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/00006231-199601000-00008","article-title":"Alpha- and beta-emitting radiolanthanides in targeted cancer therapy: The potential role of terbium-149","volume":"17","author":"Allen","year":"1996","journal-title":"Nucl. Med. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20180074","DOI":"10.1259\/bjr.20180074","article-title":"Scandium and terbium radionuclides for radiotheranostics: Current state of development towards clinical application","volume":"91","author":"Domnanich","year":"2018","journal-title":"Br. J. Radiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-57436-6","article-title":"Cross section measurements of 151Eu(3He,5n) reaction: New opportunities for medical alpha emitter 149Tb production","volume":"10","author":"Moiseeva","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2174\/1874471011666180416161908","article-title":"Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences","volume":"11","author":"Robertson","year":"2018","journal-title":"Curr. Radiopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6068","DOI":"10.1039\/c0dt01387k","article-title":"Towards translation of 212Pb as a clinical therapeutic; getting the lead in!","volume":"40","author":"Yong","year":"2011","journal-title":"Dalton Trans."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1016\/j.jmir.2019.06.051","article-title":"An appendix of radionuclides used in targeted alpha therapy","volume":"50","author":"Ferrier","year":"2019","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2174\/1874471011104030177","article-title":"Astatine-211: Production and availability","volume":"4","author":"Zalutsky","year":"2011","journal-title":"Curr. Radiopharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.1016\/j.jmir.2019.11.113","article-title":"Development of 211At production via continuous extraction of 211Rn","volume":"50","author":"Nolan","year":"2019","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"A455","DOI":"10.1007\/s10582-003-0058-z","article-title":"Terbium-149 for nuclear medicine. The production of 149Tb via heavy ions induced nuclear reactions","volume":"53","author":"Zaitseva","year":"2003","journal-title":"Czechoslov. J. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.2174\/1874471011666180502104524","article-title":"An overview of targeted alpha therapy with 225Actinium and 213Bismuth","volume":"11","author":"Morgenstern","year":"2018","journal-title":"Curr. Radiopharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2174\/1874471011666180418141357","article-title":"The production of Ac-225","volume":"11","author":"Engle","year":"2018","journal-title":"Curr. Radiopharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3934\/medsci.2015.3.228","article-title":"Application of 212Pb for Targeted \u03b1-particle Therapy (TAT): Pre-clinical and mechanistic understanding through to clinical translation","volume":"2","author":"Yong","year":"2015","journal-title":"AIMS Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.apradiso.2016.10.015","article-title":"A Radium-223 microgenerator from cyclotron-produced trace Actinium-227","volume":"119","author":"Abou","year":"2017","journal-title":"Appl. Radiat. Isot."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3390\/ph7030353","article-title":"Folate receptor targeted alpha-therapy using Terbium-149","volume":"7","author":"Reber","year":"2014","journal-title":"Pharmaceuticals"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1088\/0952-4746\/22\/3\/304","article-title":"Choice of alpha-probe operating voltage to suit a wide range of conditions","volume":"22","author":"Bosley","year":"2002","journal-title":"J. Radiol. Prot."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Crompton, A.J., Gamage, K.A.A., Jenkins, A., and Taylor, C.J. (2018). Alpha particle detection using alpha-induced air radioluminescence: A review and future prospects for preliminary radiological characterisation for nuclear facilities decommissioning. Sensors, 18.","DOI":"10.3390\/s18041015"},{"key":"ref_39","unstructured":"Sand, J., Hannuksela, V., Ihantola, S., Perajarvi, K., Toivonen, H., and Toivonen, J. (2020, July 14). Remote Optical Detection of Alpha Radiation. IAEA, International Nuclear Information System, 2010 Ref: IAEA-CN-184\/23. Available online: http:\/\/www.iaea.org\/inis\/collection\/NCLCollectionStore\/_Public\/42\/081\/42081464.pdf."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.nucmedbio.2013.01.010","article-title":"Methodology for labeling proteins and peptides with lead-212 (212Pb)","volume":"40","author":"Baidoo","year":"2013","journal-title":"Nucl. Med. Biol."},{"key":"ref_41","first-page":"166","article-title":"Bifunctional chelates for metal nuclides","volume":"52","author":"Brechbiel","year":"2007","journal-title":"Q. J. Nucl. Med. Mol. Imaging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1159\/000494760","article-title":"Targeted alpha particle therapy for neuroendocrine tumours: The next generation of peptide receptor radionuclide therapy","volume":"108","author":"Navalkissoor","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41181-019-0072-5","article-title":"Evaluation of polydentate picolinic acid chelating ligands and an \u03b1-melanocyte-stimulating hormone derivative for targeted alpha therapy using ISOL-produced 225Ac","volume":"4","author":"Ramogida","year":"2019","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19404","DOI":"10.1021\/jacs.9b10354","article-title":"Advancing chelation chemistry for actinium and other +3 f-Elements, Am, Cm, and La","volume":"141","author":"Stein","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11435","DOI":"10.1002\/chem.202002999","article-title":"Synthesis and evaluation of a new macrocyclic Actinium-225 chelator, quality control and in vivo evaluation of 225Ac-crown-\u03b1MSH peptide","volume":"26","author":"Yang","year":"2020","journal-title":"Chem. A Eur. J."},{"key":"ref_46","first-page":"1","article-title":"Efficient formation of inert Bi-213 chelates by tetraphosphorus acid analogues of DOTA: Towards improved alpha-therapeutics","volume":"8","author":"Hermann","year":"2018","journal-title":"EJNMMI Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0969-8051(97)00059-0","article-title":"212Bi-DOTMP: An alpha particle emitting bone-seeking agent for targeted radiotherapy","volume":"24","author":"Hassfjell","year":"1997","journal-title":"Nucl. Med. Biol."},{"key":"ref_48","unstructured":"Morss, L.R., Edelstein, N.M., and Fuger, J. (2008). Actinium. The Chemistry of the Actinide and Transactinide Elements, Springer."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1039\/C3CS60304K","article-title":"Matching chelators to radiometals for radiopharmaceuticals","volume":"43","author":"Price","year":"2014","journal-title":"Chem. Soc. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14712","DOI":"10.1002\/anie.201709532","article-title":"An eighteen-membered macrocyclic ligand for Actinium-225 targeted alpha therapy","volume":"56","author":"Thiele","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_51","first-page":"336","article-title":"Actinium-225 for targeted \u03b1 therapy: Coordination chemistry and current chelation approaches","volume":"33","author":"Thiele","year":"2018","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1021\/jm990141f","article-title":"Improved in vivo stability of actinium-225 macrocyclic complexes","volume":"42","author":"Deal","year":"1999","journal-title":"J. Med. Chem."},{"key":"ref_53","unstructured":"Li, L., Rousseau, J., Jaraquemada-Pel\u00e1ez, M.D.G., Wang, X., Robertson, A., Radchenko, V., Schaffer, P., Lin, K.-S., Benard, F., and Orvig, C. (2020). 225Ac-H4py4pa for targeted alpha therapy. Bioconjug. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10967-012-2238-4","article-title":"Search of ligands suitable for 212Pb\/212Bi in vivo generators","volume":"295","author":"Lyczko","year":"2013","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1016\/j.bmcl.2016.07.034","article-title":"An efficient chelator for complexation of thorium-227","volume":"26","author":"Ramdahl","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3109\/02841869609101654","article-title":"Radioimmunotherapy with \u03b1-particle emitting radioimmunoconjugates","volume":"35","author":"Zalutsky","year":"1996","journal-title":"Acta Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1021\/bc200401b","article-title":"Reagents for Astatination of Biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines","volume":"23","author":"Wilbur","year":"2012","journal-title":"Bioconjugate Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2174\/1874471010801030177","article-title":"Astatine Radiopharmaceuticals: Prospects and problems","volume":"1","author":"Vaidyanathan","year":"2008","journal-title":"Curr. Radiopharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41181-016-0008-2","article-title":"Alpha-PET with terbium-149: Evidence and perspectives for radiotheragnostics","volume":"1","author":"Vermeulen","year":"2017","journal-title":"EJNMMI Radiopharm Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13550-017-0303-2","article-title":"Pharmacokinetics, microscale distribution, and dosimetry of alpha-emitter-labeled anti-PD-L1 antibodies in an immune competent transgenic breast cancer model","volume":"7","author":"Nedrow","year":"2017","journal-title":"EJNMMI Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6145","DOI":"10.1118\/1.4965805","article-title":"Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra-223 source for targeted alpha therapy","volume":"43","author":"Staudacher","year":"2016","journal-title":"Med. Phys."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1088\/0031-9155\/57\/3\/771","article-title":"The potential for Cerenkov luminescence imaging of alpha-emitting radionuclides","volume":"57","author":"Ackerman","year":"2012","journal-title":"Phys. Med. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","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":"ref_64","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1088\/0031-9155\/56\/3\/012","article-title":"Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody","volume":"56","author":"Schwartz","year":"2011","journal-title":"Phys. Med. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s13139-017-0508-3","article-title":"Injection of botulinum toxin for preventing salivary gland toxicity after PSMA radioligand therapy: An empirical proof of a promising concept","volume":"52","author":"Baum","year":"2018","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"ref_66","doi-asserted-by":"crossref","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":"ref_67","first-page":"2841","article-title":"First in vivo evaluation of liposome-encapsulated 223Ra as a potential alpha-particle-emitting cancer therapeutic agent","volume":"26","author":"Jonasdottir","year":"2006","journal-title":"Anticancer. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1021\/bc070075t","article-title":"Enhanced retention of the \u03b1-particle-emitting daughters of actinium-225 by liposome carriers","volume":"18","author":"Sofou","year":"2007","journal-title":"Bioconjugate Chem."},{"key":"ref_69","first-page":"1","article-title":"Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy","volume":"20","author":"Pruszynski","year":"2018","journal-title":"J. Nanoparticle Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"McLaughlin, M.F., Woodward, J., Boll, R.A., Wall, J.S., Rondinone, A.J., Kennel, S.J., Mirzadeh, S., and Robertson, J.D. (2013). Gold Coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054531"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1088\/0031-9155\/55\/4\/020","article-title":"The treatment of solid tumors by alpha emitters released from224Ra-loaded sources\u2014Internal dosimetry analysis","volume":"55","author":"Arazi","year":"2010","journal-title":"Phys. Med. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1158\/0008-5472.CAN-04-3096","article-title":"Efforts to control the errant products of a targeted in vivo generator","volume":"65","author":"Jaggi","year":"2005","journal-title":"Cancer Res."},{"key":"ref_73","first-page":"54","article-title":"A pretargeting system for tumor PET imaging and radioimmunotherapy","volume":"6","author":"Erousseau","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.critrevonc.2018.01.001","article-title":"Global comparison of targeted alpha vs targeted beta therapy for cancer: In vitro, in vivo and clinical trials","volume":"123","author":"Marcu","year":"2018","journal-title":"Crit. Rev. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1007\/s00259-014-2857-9","article-title":"213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: A first-in-human experience","volume":"41","author":"Kratochwil","year":"2014","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/RLU.0000000000002915","article-title":"Peptide receptor radionuclide therapy using 225Ac-DOTATOC achieves partial remission in a patient with progressive neuroendocrine liver metastases after repeated \u03b2-emitter peptide receptor radionuclide therapy","volume":"45","author":"Zhang","year":"2020","journal-title":"Clin. Nucl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"S160","DOI":"10.1016\/j.bbmt.2019.12.714","article-title":"Preclinical development of an Actinium-225-Labeled antibody radio-conjugate directed against CD45 for targeted conditioning and radioimmunotherapy","volume":"26","author":"Ludwig","year":"2020","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kasten, B.B., Oliver, P., Kim, H., Fan, J., Ferrone, S., Zinn, K.R., and Buchsbaum, D.J. (2018). 212Pb-labeled antibody 225.28 targeted to chondroitin sulfate proteoglycan 4 for triple-negative breast cancer therapy in mouse models. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040925"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1158\/1078-0432.CCR-19-1485","article-title":"Investigating PSMA-targeted radioligand therapy efficacy as a function of cellular PSMA levels and intratumoral PSMA heterogeneity","volume":"26","author":"Current","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1158\/1078-0432.CCR-19-2268","article-title":"Preclinical efficacy of a PSMA-targeted thorium-227 Conjugate (PSMA-TTC), a targeted alpha therapy for prostate cancer","volume":"26","author":"Hammer","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.2967\/jnumed.115.171371","article-title":"Vascular targeted radioimmunotherapy for the treatment of glioblastoma","volume":"57","author":"Behling","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_82","first-page":"614","article-title":"Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma","volume":"46","author":"Bruchertseifer","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2967\/jnumed.107.046938","article-title":"Clinical experience with alpha-Particle Emitting 211At: Treatment of recurrent brain tumor patients with 211At-Labeled chimeric antitenascin monoclonal antibody 81C6","volume":"49","author":"Zalutsky","year":"2007","journal-title":"J. Nucl. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1182\/blood-2010-05-282327","article-title":"Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: A preclinical model toward optimal consolidation therapy to eradicate minimal residual disease","volume":"116","author":"Park","year":"2010","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00259-009-1197-7","article-title":"Assessment of long-term radiotoxicity after treatment with the low-dose-rate alpha-particle-emitting radioimmunoconjugate 227Th-rituximab","volume":"37","author":"Dahle","year":"2009","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1158\/1535-7163.MCT-16-0251","article-title":"In vitro and in vivo efficacy of a novel CD33-Targeted Thorium-227 conjugate for the treatment of acute myeloid leukemia","volume":"15","author":"Hagemann","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Jurcic, J.G., and Rosenblat, T.L. (2014). Targeted alpha-particle immunotherapy for acute myeloid leukemia. Am. Soc. Clin. Oncol. Educ. Book, e126\u2013e131.","DOI":"10.14694\/EdBook_AM.2014.34.e126"},{"key":"ref_88","first-page":"3120","article-title":"Significant antitumor effect from bone-seeking, alpha-particle-emitting (223)Ra demonstrated in an experimental skeletal metastases model","volume":"62","author":"Henriksen","year":"2002","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/jlcr.3610","article-title":"Ra-224 labeling of calcium carbonate microparticles for internal \u03b1-therapy: Preparation, stability, and biodistribution in mice","volume":"61","author":"Malenge","year":"2018","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.nucmedbio.2017.12.004","article-title":"212Pb-labeled B7-H3-targeting antibody for pancreatic cancer therapy in mouse models","volume":"58","author":"Kasten","year":"2018","journal-title":"Nucl. Med. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.bmc.2018.01.023","article-title":"Evaluation of astatine-211-labeled octreotide as a potential radiotherapeutic agent for NSCLC treatment","volume":"26","author":"Zhao","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1111\/cas.13636","article-title":"\u03b1-particle therapy for synovial sarcoma in the mouse using an astatine-211-labeled antibody against frizzled homolog 10","volume":"109","author":"Li","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1007\/s00259-018-4003-6","article-title":"Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: A pilot study","volume":"45","author":"Autenrieth","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.ijrobp.2019.10.048","article-title":"Initial safety and tumor control results from a \u201cFirst-in-Human\u201d multicenter prospective trial evaluating a novel alpha-emitting radionuclide for the treatment of locally advanced recurrent squamous cell carcinomas of the skin and head and neck","volume":"106","author":"Popovtzer","year":"2020","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1021\/acs.molpharmaceut.7b00985","article-title":"Evaluation of an Anti-HER2 nanobody labeled with 225Ac for targeted \u03b1-Particle therapy of cancer","volume":"15","author":"Bruchertseifer","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fmed.2015.00076","article-title":"Single-Dose Anti-CD138 radioimmunotherapy: Bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model","volume":"2","author":"Fichou","year":"2015","journal-title":"Front. Med."},{"key":"ref_97","first-page":"6095","article-title":"An alpha-particle emitting antibody ([213Bi]J591) for radioimmunotherapy of prostate cancer","volume":"60","author":"McDevitt","year":"2000","journal-title":"Cancer Res."},{"key":"ref_98","first-page":"1435","article-title":"Alpharadin-Therapie bei Patienten mit metastasiertem kastrationsrefrakt\u00e4rem Prostatakarzinom Radium-223 dichloride in patients with castration-refractory prostate cancer","volume":"56","author":"Winter","year":"2017","journal-title":"Der Urol."},{"key":"ref_99","first-page":"1947","article-title":"Antitumor activity of novel bone-seeking, \u03b1-emitting 224Ra-solution in a breast cancer skeletal metastases model","volume":"38","author":"Juzeniene","year":"2018","journal-title":"Anticancer. Res."},{"key":"ref_100","first-page":"5315","article-title":"Intratumoral 224Ra-loaded wires spread alpha-emitters inside solid human tumors in athymic mice achieving tumor control","volume":"32","author":"Cooks","year":"2012","journal-title":"Anticancer. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2967\/jnumed.119.229393","article-title":"Preclinical evaluation of 203\/212Pb-Labeled low-molecular-weight compounds for targeted radiopharmaceutical therapy of prostate cancer","volume":"61","author":"Banerjee","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Boudousq, V., Bobyk, L., Busson, M., Garambois, V., Jarlier, M., Charalambatou, P., P\u00e8legrin, A., Paillas, S., Chouin, N., and Quenet, F. (2013). Comparison between Internalizing Anti-HER2 mAbs and Non-Internalizing Anti-CEA mAbs in Alpha-radioimmunotherapy of small volume peritoneal carcinomatosis using 212Pb. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069613"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jlcr.3825","article-title":"Preparation of the alpha-emitting prostate-specific membrane antigen targeted radioligand [212 Pb]Pb-NG001 for prostate cancer","volume":"63","author":"Stenberg","year":"2020","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.nucmedbio.2017.09.003","article-title":"Astatine-211 labeled anti-HER2 5F7 single domain antibody fragment conjugates: Radiolabeling and preliminary evaluation","volume":"56","author":"Choi","year":"2017","journal-title":"Nucl. Med. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3524","DOI":"10.1021\/acs.molpharmaceut.9b00354","article-title":"Labeling of Anti-HER2 Nanobodies WITH Astatine-211: Optimization and the effect of different coupling reagents on their in vivo behavior","volume":"16","author":"Dekempeneer","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1182\/blood.2019001250","article-title":"The \u03b1-emitter astatine-211 targeted to CD38 can eradicate multiple myeloma in a disseminated disease model","volume":"134","author":"Comstock","year":"2019","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.bbrc.2018.10.157","article-title":"Targeted cancer cell ablation in mice by an \u03b1-particle-emitting astatine-211-labeled antibody against major histocompatibility complex class I chain-related protein A and B","volume":"506","author":"Li","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00259-003-1413-9","article-title":"Targeted alpha therapy in vivo: Direct evidence for single cancer cell kill using 149Tb-rituximab","volume":"31","author":"Beyer","year":"2004","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00259-017-3751-z","article-title":"177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer","volume":"44","author":"Grubert","year":"2017","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1053\/j.semnuclmed.2020.02.004","article-title":"225Ac-PSMA-617 for Therapy of Prostate Cancer","volume":"50","author":"Kratochwil","year":"2020","journal-title":"Semin. Nucl. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00259-018-4167-0","article-title":"225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: A pilot study","volume":"46","author":"Sathekge","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4451","DOI":"10.1158\/1078-0432.CCR-04-2244","article-title":"First Clinical Experience with alpha-Emitting Radium-223 in the Treatment of Skeletal Metastases","volume":"11","author":"Nilsson","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/S1470-2045(14)70183-4","article-title":"Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: Results from a phase 3, double-blind, randomised trial","volume":"15","author":"Sartor","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1213755","article-title":"Alpha emitter radium-223 and survival in metastatic prostate cancer","volume":"369","author":"Parker","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_115","unstructured":"European Medicines Agency (2018, November 11). EMA Restricts Use of Prostate Cancer Medicine Xofigo. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/xofigo."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.2967\/jnumed.114.143842","article-title":"Dose escalation and dosimetry of first-in-human \u03b1 radioimmunotherapy with 212Pb-TCMC-trastuzumab","volume":"55","author":"Meredith","year":"2014","journal-title":"J. Nucl. Med."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Li, Y., Hamlin, D.K., Chyan, M.-K., Wong, R., Dorman, E.F., Emery, R.C., Woodle, D.R., Manger, R.L., Nartea, M., and Kenoyer, A.L. (2018). cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205135"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2967\/jnumed.109.062604","article-title":"Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: Pharmacokinetics and dosimetry of 211At-MX35 F(ab\u2019)2\u2014A phase I study","volume":"50","author":"Andersson","year":"2009","journal-title":"J. Nucl. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/1\/49\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:30Z","timestamp":1760179710000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/1\/49"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,31]]},"references-count":118,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["pharmaceutics13010049"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13010049","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,31]]}}}