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Adv."],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:p>\n                    Therapeutic antibodies and antibody-drug conjugates are limited by large molecular size, poor tumor penetration, and signaling-adaptive resistance. We introduce an engineering strategy for radiotherapeutic antibody fragments in which an albumin-binding domain (ABD) rebalances molecular size and pharmacokinetics. Using human epidermal growth factor receptor 2 (HER2) as a proof of concept, we developed\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-Fab-ABD, which integrates rapid tumor penetration with albumin-mediated extended circulation, improving tumor dosimetry while reducing off-target radiation. In HER2 tumor models,\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-Fab-ABD showed strong HER2 and albumin binding, reduced off-target retention, and substantially lower hematologic toxicity than full-length\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-pertuzumab while maintaining potent \u03b2-particle tumor control. It also overcame intrinsic trastuzumab resistance by bypassing receptor blockade and inducing DNA double-strand breaks and displayed mechanistic complementarity with trastuzumab. Overall,\n                    <jats:sup>177<\/jats:sup>\n                    Lu-DOTA-Fab-ABD represents a generalizable framework for engineering fragment\u2013based radiotherapeutics.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee4052","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:58:48Z","timestamp":1784311128000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Albumin binding improves the pharmacokinetics and therapeutic efficacy of a\n                    <sup>177<\/sup>\n                    Lu-labeled HER2 Fab radioconjugate"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9707-7810","authenticated-orcid":true,"given":"Peifei","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Nuclear Medicine and Molecular Imaging, Shandong Cancer Hospital and Institute, Jinan 250117, China."},{"name":"Center for 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