{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:08:13Z","timestamp":1788772093855,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Targeted Alpha Therapy (TAT) is often defined by the favorable physical properties of alpha particles, particularly their high linear energy transfer and short tissue range. However, these properties alone do not determine therapeutic success. The clinical behavior of alpha-emitting radiopharmaceuticals depends on whether radioactive decay can be matched to an appropriate biological scale and maintained within a chemically and pharmacokinetically coherent system. This review presents TAT as a multiscale design problem in which radionuclide production, radioactive decay, recoil, coordination chemistry, vector compatibility, tissue geometry, microdosimetry, biodistribution, and clinical outcome are interdependent rather than separate considerations. Established and emerging alpha emitters, including radium-223, astatine-211, lead-212\/bismuth-212, actinium-225\/bismuth-213, thorium-227 and terbium-149, are examined as distinct design solutions rather than interchangeable therapeutic options. Their comparison shows that no single radionuclide is universally optimal, as each occupies a distinct position within a landscape defined by physical, chemical and biological constraints. Viewing TAT as a multiscale design problem shifts radionuclide selection from the search for a universally superior emitter toward the rational matching of radionuclide properties to therapeutic context.<\/jats:p>","DOI":"10.3390\/ph19091403","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Alpha Therapy as a Multiscale Design Problem: From Radioactive Decay to Therapeutic Outcome"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9790-7820","authenticated-orcid":false,"given":"Isidora","family":"Lazi\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1680-4260","authenticated-orcid":false,"given":"Aljo\u0161a","family":"Stankovi\u0107","sequence":"additional","affiliation":[{"name":"Clinical Department of Nuclear Medicine and Thyroid Gland Disease, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Department for Pharmaceutical Technology and Cosmetology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1519-5643","authenticated-orcid":false,"given":"Nemanja","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofija","family":"Forkapi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physics, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-3868","authenticated-orcid":false,"given":"Mladena","family":"Lali\u0107-Popovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine Novi Sad, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20503121211034366","DOI":"10.1177\/20503121211034366","article-title":"New approaches and procedures for cancer treatment: Current perspectives","volume":"9","author":"Debela","year":"2021","journal-title":"SAGE Open Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Garg, P., Malhotra, J., Kulkarni, P., Horne, D., Salgia, R., and Singhal, S.S. (2024). Emerging therapeutic strategies to overcome drug resistance in cancer cells. Cancers, 16.","DOI":"10.3390\/cancers16132478"},{"key":"ref_3","unstructured":"National Research Council (US), and Institute of Medicine (US) Committee on State of the Science of Nuclear Medicine (2007). Nuclear medicine. Advancing Nuclear Medicine Through Innovation, National Academies Press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20150042","DOI":"10.1259\/bjr.20150042","article-title":"Improving external beam radiotherapy by combination with internal irradiation","volume":"88","author":"Dietrich","year":"2015","journal-title":"Br. J. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stokke, C., Kvassheim, M., and Blakkisrud, J. (2022). Radionuclides for targeted therapy: Physical properties. Molecules, 27.","DOI":"10.3390\/molecules27175429"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nelson, B.J.B., Andersson, J.D., and Wuest, F. (2021). Targeted alpha therapy: Progress in radionuclide production, radiochemistry, and applications. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010049"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Miederer, M., Bene\u0161ov\u00e1-Sch\u00e4fer, M., Mamat, C., K\u00e4stner, D., Pretze, M., Michler, E., Brogsitter, C., Kotzerke, J., Kopka, K., and Scheinberg, D.A. (2024). Alpha-emitting radionuclides: Current status and future perspectives. Pharmaceuticals, 17.","DOI":"10.3390\/ph17010076"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jang, A., Kendi, A.T., Johnson, G.B., Halfdanarson, T.R., and Sartor, O. (2023). Targeted Alpha-Particle Therapy: A Review of Current Trials. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411626"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s00259-025-07390-0","article-title":"Targeted alpha therapy: A comprehensive analysis of the biological effects from \u201clocal-regional-systemic\u201d dimensions","volume":"53","author":"Song","year":"2025","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108990","DOI":"10.1016\/j.nucmedbio.2024.108990","article-title":"Alpha Atlas: Mapping global production of \u03b1-emitting radionuclides for targeted alpha therapy","volume":"142\u2013143","author":"Tosato","year":"2025","journal-title":"Nucl. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Eychenne, R., Ch\u00e9rel, M., Haddad, F., Gu\u00e9rard, F., and Gestin, J.F. (2021). Overview of the most promising radionuclides for targeted alpha therapy: The \u201cHopeful Eight\u201d. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060906"},{"key":"ref_12","unstructured":"Baum, R.P. (2013). Therapeutic radionuclides: Production, physical characteristics, and applications. Therapeutic Nuclear Medicine, Springer."},{"key":"ref_13","unstructured":"L\u2019Annunziata, M.F. (2016). Radioactivity: Introduction and History, from the Quantum to Quarks, Elsevier. [2nd ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","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_15","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.addr.2008.04.007","article-title":"Alpha-particles for targeted therapy","volume":"60","author":"Sgouros","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1053\/j.semnuclmed.2008.05.002","article-title":"Therapeutic radionuclides: Biophysical and radiobiologic principles","volume":"38","author":"Kassis","year":"2008","journal-title":"Semin. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1088\/0031-9155\/41\/10\/009","article-title":"Targeted radiotherapy using Auger electron emitters","volume":"41","author":"Wheldon","year":"1996","journal-title":"Phys. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/09553002.2020.1831706","article-title":"Advancements in the use of Auger electrons in science and medicine during the period 2015\u20132019","volume":"99","author":"Howell","year":"2023","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Attix, F.H. (1986). Charged-particle interactions in matter. Introduction to Radiological Physics and Radiation Dosimetry, John Wiley & Sons.","DOI":"10.1002\/9783527617135"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mayles, W.P.M., Nahum, A.E., and Rosenwald, J.C. (2021). Handbook of Radiotherapy Physics: Theory and Practice, CRC Press. [2nd ed.].","DOI":"10.1201\/9780429201493"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"McParland, B.J. (2010). Charged particle interactions with matter. Nuclear Medicine Radiation Dosimetry: Advanced Theoretical Principles, Springer.","DOI":"10.1007\/978-1-84882-126-2_7"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s002590050366","article-title":"Three-step radioimmunotherapy with yttrium-90 biotin: Dosimetry and pharmacokinetics in cancer patients","volume":"26","author":"Cremonesi","year":"1999","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1088\/0031-9155\/53\/7\/007","article-title":"Cross-fire doses from beta-emitting radionuclides in targeted radiotherapy: A theoretical study based on experimentally measured tumor characteristics","volume":"53","author":"Enger","year":"2008","journal-title":"Phys. Med. Biol."},{"key":"ref_24","unstructured":"Nakashima, J., and Duong, H. (2026). Radiation physics in medicine. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_25","unstructured":"Petrovi\u0107, B. (2018). Fizi\u010dke Osnove Radioterapije [Physical Foundations of Radiotherapy], Univerzitet u Novom Sadu, Prirodno-matemati\u010dki fakultet, Departman za fiziku."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4103\/0973-1482.73324","article-title":"External and internal radiation therapy: Past and future directions","volume":"6","author":"Sadeghi","year":"2010","journal-title":"J. Cancer Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24785","DOI":"10.1021\/acs.jmedchem.5c02063","article-title":"\u03b1 Emitter-labeled radiopeptides for targeted \u03b1 therapy of tumors","volume":"68","author":"Cieslik","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tafreshi, N.K., Doligalski, M.L., Tichacek, C.J., Pandya, D.N., Budzevich, M.M., El-Haddad, G., Khushalani, N.I., Moros, E.G., McLaughlin, M.L., and Wadas, T.J. (2019). Development of targeted alpha particle therapy for solid tumors. Molecules, 24.","DOI":"10.3390\/molecules24234314"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pouget, J.-P., and Constanzo, J. (2021). Revisiting the radiobiology of targeted alpha therapy. Front. Med., 8.","DOI":"10.3389\/fmed.2021.692436"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1053\/j.semnuclmed.2019.11.002","article-title":"Dosimetry, radiobiology and synthetic lethality: Radiopharmaceutical therapy (RPT) with alpha-particle emitters","volume":"50","author":"Sgouros","year":"2020","journal-title":"Semin. Nucl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00411-019-00826-w","article-title":"Internal microdosimetry of alpha-emitting radionuclides","volume":"59","author":"Hofmann","year":"2020","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1140\/epjp\/s13360-024-05318-5","article-title":"On the radiation quality characterization in radiation therapy: From linear energy transfer to experimental microdosimetry","volume":"139","author":"Missiaggia","year":"2024","journal-title":"Eur. Phys. J. Plus"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"153212","DOI":"10.1155\/2012\/153212","article-title":"Microdosimetry for targeted alpha therapy of cancer","volume":"2012","author":"Huang","year":"2012","journal-title":"Comput. Math. Methods Med."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"09TR01","DOI":"10.1088\/1361-6560\/ac5fe0","article-title":"Dosimetry in targeted alpha therapy. A systematic review: Current findings and what is needed","volume":"67","author":"Tronchin","year":"2022","journal-title":"Phys. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100018","DOI":"10.1016\/j.eanmi.2025.100018","article-title":"EANM recommendations for dosimetry in targeted radionuclide therapy with alpha-emitters","volume":"2","author":"Chouin","year":"2026","journal-title":"EANM Innov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40658-020-00350-7","article-title":"Individual dosimetry system for targeted alpha therapy based on PHITS coupled with microdosimetric kinetic model","volume":"8","author":"Sato","year":"2021","journal-title":"EJNMMI Phys."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40658-026-00847-7","article-title":"Recent advances and current landscape of software tools for image analysis and dosimetry in nuclear medicine","volume":"13","author":"Banda","year":"2026","journal-title":"EJNMMI Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.2967\/jnumed.121.263253","article-title":"MIRD Pamphlet No. 27: MIRDcell V3, a revised software tool for multicellular dosimetry and bioeffect modeling","volume":"63","author":"Katugampola","year":"2022","journal-title":"J. Nucl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pallares, R.M., and Abergel, R.J. (2022). Development of radiopharmaceuticals for targeted alpha therapy: Where do we stand?. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1020188"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Palangka, C.R.A.P., Mahendra, I., Ritawidya, R., Kondo, N., and Nakajima, T. (2025). Alpha particle emitter radiolabeled antibodies in cancer therapy: Current status, challenges, and future prospects. Pharmaceuticals, 18.","DOI":"10.3390\/ph18091316"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1515\/ract-2019-0005","article-title":"Radiochemical aspects of alpha emitting radionuclides for medical application","volume":"107","author":"Ferrier","year":"2019","journal-title":"Radiochim. Acta"},{"key":"ref_43","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_44","doi-asserted-by":"crossref","unstructured":"Conte, M., Tomaciello, M., De Feo, M.S., Frantellizzi, V., Marampon, F., De Cristofaro, F., De Vincentis, G., and Filippi, L. (2025). The tight relationship between the tumoral microenvironment and radium-223. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020456"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0969-8043(01)00282-2","article-title":"Evaluation of potential chelating agents for radium","volume":"56","author":"Henriksen","year":"2002","journal-title":"Appl. Radiat. Isot."},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"104819","DOI":"10.1016\/j.critrevonc.2025.104819","article-title":"A new era for radium-223? Optimizing treatment by balancing efficacy and toxicity through combination therapies","volume":"214","author":"Farinea","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lin, S.C., Yu, G., Corn, P.G., Damasco, J., Lee, Y.-C., Song, J.H., Navone, N.M., Logothetis, C.J., Melancon, M.P., and Panaretakis, T. (2024). Radium-223 treatment produces prolonged suppression of resident osteoblasts and decreased bone mineral density in trabecular bone in osteoblast reporter mice. Cancers, 16.","DOI":"10.3390\/cancers16142603"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1093\/jrr\/rrx026","article-title":"Differences in responses to X-ray exposure between osteoclast and osteoblast cells","volume":"58","author":"Zhang","year":"2017","journal-title":"J. Radiat. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1140\/epjp\/s13360-024-05319-4","article-title":"Investigation of 209Bi(\u03b1,2n)211At reaction route for the production of \u03b1-emitter 211At","volume":"139","author":"Kaplan","year":"2024","journal-title":"Eur. Phys. J. Plus"},{"key":"ref_51","first-page":"425","article-title":"Realizing clinical trials with astatine-211: The chemistry infrastructure","volume":"35","author":"Lindegren","year":"2020","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_52","first-page":"1","article-title":"Production of [211At]-astatinated radiopharmaceuticals and applications in targeted \u03b1-particle therapy","volume":"28","author":"Gestin","year":"2013","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"109573","DOI":"10.1016\/j.nucmedbio.2025.109573","article-title":"Recent advances in understanding and improving the stability of 211At-radiopharmaceuticals","volume":"150\u2013151","author":"Fouinneteau","year":"2025","journal-title":"Nucl. Med. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3724\/abbs.2024206","article-title":"Astatine-211 and actinium-225: Two promising nuclides in targeted alpha therapy","volume":"57","author":"Zuo","year":"2025","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.tips.2026.01.001","article-title":"Targeted alpha therapy (r)evolution: Emerging nuclides for clinical applications","volume":"47","author":"Pedersen","year":"2026","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2967\/jnumed.109.062604","article-title":"Intraperitoneal \u03b1-particle radioimmunotherapy of ovarian cancer patients: Pharmacokinetics and dosimetry of 211At-MX35 F(ab\u2032)2\u2014A phase I study","volume":"50","author":"Andersson","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.2967\/jnumed.118.220384","article-title":"Intraperitoneal \u03b1-emitting radioimmunotherapy with 211At in relapsed ovarian cancer: Long-term follow-up with individual absorbed dose estimations","volume":"60","author":"Hallqvist","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.2967\/jnumed.125.270810","article-title":"First-in-human study of [211At]NaAt as targeted \u03b1-therapy in patients with radioiodine-refractory thyroid cancer (Alpha-T1 Trial)","volume":"66","author":"Watabe","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1248\/yakushi.25-00146-4","article-title":"Clinical application of targeted alpha therapy using astatine","volume":"146","author":"Watabe","year":"2026","journal-title":"Yakugaku Zasshi"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.7150\/thno.126086","article-title":"Lead radionuclides for theranostic applications in nuclear medicine: From atom to bedside","volume":"16","author":"Berckmans","year":"2026","journal-title":"Theranostics"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Di Iorio, V., Sarnelli, A., Boschi, S., Sansovini, M., Genovese, R.M., Stefanescu, C., Ghizdovat, V., Jalloul, W., Young, J., and Sosabowski, J. (2025). Recommendations on the clinical application and future potential of \u03b1-particle therapy: A comprehensive review of the results from the SECURE Project. Pharmaceuticals, 18.","DOI":"10.20944\/preprints202508.0853.v1"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s41181-025-00362-7","article-title":"212Pb in targeted radionuclide therapy: A review","volume":"10","author":"Abell","year":"2025","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"570831","DOI":"10.2147\/DDDT.S570831","article-title":"Radiopharmaceutical: An update and comparison of preclinical investigation result of alpha and beta emitter radioisotope","volume":"20","author":"Luhung","year":"2026","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Leupe, H., Cauwenbergh, M., Cleeren, F., Dekervel, J., Verslype, C., and Deroose, C.M. (2025). Clinical experience with targeted alpha-emitter peptide receptor radionuclide therapy (\u03b1-PRRT) for somatostatin receptor-positive neuroendocrine tumors. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111608"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ramonaheng, K., Banda, K., Qebetu, M., Goorhoo, P., Legodi, K., Masogo, T., Seebarruth, Y., Mdanda, S., Sibiya, S., and Mzizi, Y. (2026). Clinical image-based dosimetry of actinium-225 in targeted alpha therapy. Cancers, 18.","DOI":"10.3390\/cancers18020321"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Nawar, M.F., Selim, A.A., Essa, B.M., El-Daoushy, A.F., Swidan, M.M., Chambers, C.G., Al Qahtani, M.H., Smith, C.J., and Sakr, T.M. (2025). Actinium-225\/bismuth-213 as potential leaders for targeted alpha therapy: Current supply, application barriers, and future prospects. Cancers, 17.","DOI":"10.3390\/cancers17183055"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s12149-025-02117-5","article-title":"Clinical perspective on targeted alpha therapy using 225Ac","volume":"39","author":"Lim","year":"2025","journal-title":"Ann. Nucl. Med."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rizzo, A., Imperiale, A., Annunziata, S., Delgado Bolton, R.C., Albano, D., Fiz, F., Piccardo, A., Cuzzocrea, M., Paone, G., and Treglia, G. (2025). Efficacy and safety of radioligand therapy with actinium-225 DOTATATE in patients with advanced, metastatic or inoperable neuroendocrine neoplasms: A systematic review and meta-analysis. Medicina, 61.","DOI":"10.3390\/medicina61081341"},{"key":"ref_69","first-page":"500161","article-title":"State of the art and future perspectives of new radionuclides in nuclear medicine: Part III","volume":"44","author":"Torres","year":"2025","journal-title":"Rev. Esp. Med. Nucl. Imagen Mol. Engl. Ed."},{"key":"ref_70","first-page":"420","article-title":"An integrated analysis of four targeted thorium conjugates to assess the 227Th and 223Ra distribution and tissue-related radiation","volume":"41","author":"Block","year":"2026","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Karlsson, J., Schatz, C.A., Wengner, A.M., Hammer, S., Scholz, A., Cuthbertson, A., Wagner, V., Hennekes, H., Jardine, V., and Hagemann, U.B. (2023). Targeted thorium-227 conjugates as treatment options in oncology. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1071086"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Anderson, P.M., Subbiah, V., and Trucco, M.M. (2022). Current and future targeted alpha particle therapies for osteosarcoma: Radium-223, actinium-225, and thorium-227. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1030094"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"105905","DOI":"10.1016\/j.esmoop.2025.105905","article-title":"First-in-human study of a thorium-227-labeled mesothelin-targeting antibody-chelator conjugate (MSLN-TTC), in patients with malignant mesothelioma and other solid tumors","volume":"10","author":"Minchom","year":"2025","journal-title":"ESMO Open"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1053\/j.semnuclmed.2023.06.007","article-title":"Preclinical development in radiopharmaceutical therapy for prostate cancer","volume":"53","author":"Alati","year":"2023","journal-title":"Semin. Nucl. Med."},{"key":"ref_75","first-page":"500128","article-title":"State of the art and future perspectives of new radionuclides in nuclear medicine. Part II","volume":"44","author":"Sancho","year":"2025","journal-title":"Rev. Esp. Med. Nucl. Imagen Mol. Engl. Ed."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.7150\/thno.92775","article-title":"Terbium radionuclides for theranostic applications in nuclear medicine: From atom to bedside","volume":"14","author":"Koole","year":"2024","journal-title":"Theranostics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s00259-024-07035-8","article-title":"Preclinical investigation of [149Tb]Tb-DOTATATE and [149Tb]Tb-DOTA-LM3 for tumor-targeted alpha therapy","volume":"52","author":"Mapanao","year":"2025","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s00259-024-06719-5","article-title":"Can current preclinical strategies for radiopharmaceutical development meet the needs of targeted alpha therapy?","volume":"51","author":"Kleynhans","year":"2024","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1016\/j.apsb.2025.09.039","article-title":"Artificial intelligence for radiopharmaceutical and molecular imaging","volume":"15","author":"Tao","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s13139-026-00988-8","article-title":"Personalised dosimetry in nuclear medicine: Bridging physics, biology and AI for next generation radiopharmaceutical therapy","volume":"60","author":"Shanmugiah","year":"2026","journal-title":"Nucl. Med. Mol. Imaging"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:13:08Z","timestamp":1788768788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":80,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ph19091403"],"URL":"https:\/\/doi.org\/10.3390\/ph19091403","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}