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This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [<jats:sup>177<\/jats:sup>Lu]Lu-PSMA-I&amp;T in an orthotopic model of TNBC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Rj:NMRI-<jats:italic>Foxn1<\/jats:italic><jats:sup><jats:italic>nu\/nu<\/jats:italic><\/jats:sup> mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1\u2009\u00d7\u200960\u2009\u00b1\u20095\u00a0MBq dose of [<jats:sup>177<\/jats:sup>Lu]Lu-PSMA-I&amp;T, while the fractionated dose group received 4\u2009\u00d7 a 15\u2009\u00b1\u20092\u00a0MBq dose of [<jats:sup>177<\/jats:sup>Lu]Lu-PSMA-I&amp;T at 7\u00a0day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [<jats:sup>18<\/jats:sup>F]FDG-PET\/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&amp;E staining, microautoradiography, and autoradiography.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Tumor volumes were significantly smaller in the single dose (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and fractionated dose (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [<jats:sup>177<\/jats:sup>Lu]Lu-PSMA-I&amp;T decreased the size of viable tumor areas. We further demonstrated, that [<jats:sup>177<\/jats:sup>Lu]Lu-PSMA-I&amp;T binds specifically to the tumor-associated vasculature.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study highlights the potential of [<jats:sup>177<\/jats:sup>Lu]Lu-PSMA-I&amp;T for endogenous radiotherapy of TNBC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13058-024-01787-9","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T10:02:39Z","timestamp":1708423359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I&amp;T for triple-negative breast cancer"],"prefix":"10.1186","volume":"26","author":[{"given":"Amelie","family":"Heesch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru","family":"Florea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pardes","family":"Habib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura S.","family":"Werth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmar","family":"Stickeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabri E. 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