{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:56:16Z","timestamp":1790034976969,"version":"4.0.1"},"reference-count":63,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["569665351"],"award-info":[{"award-number":["569665351"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"award":["569665351"],"award-info":[{"award-number":["569665351"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Auger-electron-emitting radionuclides offer a distinctive route toward molecular-scale radiotherapy because their biological effects depend primarily on the nanoscale location of the decay event rather than on long-range tissue penetration. This review examines Auger-emitting radionuclides from a radiopharmaceutical perspective, integrating decay-associated physicochemical processes, cellular dosimetry, subcellular targeting, and translational relevance. We first discuss the physical determinants of Auger radiotoxicity, including Auger and Coster\u2013Kronig electrons, internal-conversion electrons, local ionization density, and possible molecular consequences of highly localized Auger cascades. Cellular S values are used to illustrate how the same radionuclide can produce markedly different absorbed doses depending on whether activity is localized in the nucleus, cytoplasm, cell membrane, or neighboring cells. Iodine-125 incorporated into DNA as [125I]iododeoxyuridine ([125I]IUdR) remains the classical reference model for maximal Auger-mediated radiotoxicity. However, this direct DNA-incorporation model should not be generalized to receptor-targeted radiopharmaceuticals, which usually achieve indirect nuclear, chromatin-associated, perinuclear, membrane-associated, or vesicular localization rather than incorporation into DNA. These alternative source\u2013target geometries may also produce biologically relevant effects, but they are mechanistically distinct from DNA-proximal [125I]IUdR decay. Particular attention is given to iodine-123 versus iodine-125, the influence of physical half-life and specific activity, the interpretation of terbium-161 as a hybrid \u03b2\u2212\/internal-conversion\/Auger emitter, and the overlooked radiobiological relevance of diagnostic Auger emitters such as technetium-99m, indium-111, and gallium-67. We conclude that Auger-emitter radiopharmaceuticals cannot be ranked by electron yield or decay scheme alone. Their therapeutic or toxicological relevance emerges from the integration of decay-associated physicochemical processes, cellular source\u2013target dosimetry, intracellular trafficking, retention, and the temporal realization of dose delivery.<\/jats:p>","DOI":"10.3390\/ijms27146445","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"6445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Auger-Emitting Radionuclides in Radiopharmaceutical Research: Decay-Associated Processes, Vector-Dependent Localization, and Translational Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2636-0058","authenticated-orcid":false,"given":"Klaus","family":"Schom\u00e4cker","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand","family":"Sudbrock","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Freifrau von Brandenstein","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-9412","authenticated-orcid":false,"given":"Baki","family":"Akg\u00fcl","sequence":"additional","affiliation":[{"name":"Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50935 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4106-0520","authenticated-orcid":false,"given":"Martin","family":"Hufbauer","sequence":"additional","affiliation":[{"name":"Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50935 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6118-5182","authenticated-orcid":false,"given":"Thomas","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabri E. M.","family":"Sahnoun","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-7155","authenticated-orcid":false,"given":"Felix","family":"Dietlein","sequence":"additional","affiliation":[{"name":"Computational Health Informatics Program, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Krapf","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"},{"name":"Nuclear Chemistry (INM-5), Institute of Neuroscience and Medicine, Forschungszentrum J\u00fclich GmbH, Wilhelm-Johnen-Stra\u00dfe, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0992-6099","authenticated-orcid":false,"given":"Markus","family":"Dietlein","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Drzezga","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany"},{"name":"Nuclear Chemistry (INM-5), Institute of Neuroscience and Medicine, Forschungszentrum J\u00fclich GmbH, Wilhelm-Johnen-Stra\u00dfe, 52428 J\u00fclich, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Venusberg-Campus 1\/99, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","first-page":"1007","article-title":"Theranostics in Perspective: White Paper","volume":"66","author":"Stokkel","year":"2025","journal-title":"J. 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