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Leveraging the complementary theranostic targets fibroblast activation protein (FAP) and Nectin\u20104, we designed the novel hetero\u2010bivalent agent FZ\u2010NF\u20101 for dual targeting. Preclinically, both\n                    <jats:sup>68<\/jats:sup>\n                    Ga\u2010labeled and\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010labeled FZ\u2010NF\u20101 exhibited high radiochemical purity, good stability, and high affinity for both Nectin\u20104 and FAP.\n                    <jats:sup>68<\/jats:sup>\n                    Ga\u2010FZ\u2010NF\u20101 revealed better tumor uptake and prolonged retention time compared to monomeric FAP\u2010 or Nectin\u20104 targeted tracers. Moreover,\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010FZ\u2010NF\u20101 exhibited sustained tumor accumulation for upto 120 h post\u2010injection, leading to significant, dose\u2010dependent tumor regression in TNBC mouse models, with no obvious systemic toxicity observed. In a preliminary first\u2010in\u2010human translational study involving 13 patients with TNBC,\n                    <jats:sup>68<\/jats:sup>\n                    Ga\u2010FZ\u2010NF\u20101 demonstrated comparable tumor uptake to that of\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010fluorodeoxyglucose (\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010FDG), while successfully identifying additional lesions missed by\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010FDG. Complementary tissue microarray analysis of 60 TNBC cases confirmed the heterogeneous expression of Nectin\u20104 and FAP in TNBC. By concurrently targeting the tumor cells and stroma,\n                    <jats:sup>68<\/jats:sup>\n                    Ga\/\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010FZ\u2010NF\u20101 effectively mitigates the limitations associated with single\u2010target imaging and therapy. These results indicate that the heterodimeric theranostic pair offers enhanced imaging performance and significant therapeutic efficacy, providing a promising strategy for the personalized management of refractory TNBC.\n                  <\/jats:p>","DOI":"10.1002\/advs.77606","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:35:46Z","timestamp":1788928546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual\u2010Target Nectin\u20104\/FAP Heterobivalent Probe\n                    <sup>68<\/sup>\n                    Ga\/\n                    <sup>177<\/sup>\n                    Lu\u2010FZ\u2010NF\u20101 for Triple\u2010Negative Breast Cancer: Preclinical Theranostic Evaluation and First\u2010in\u2010Human Translation"],"prefix":"10.1002","author":[{"given":"Ye","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Fudan University Shanghai Cancer Center  Shanghai P. 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