<i>In vitro</i> binding specificity, <i>in vivo</i> tumor targeting, biodistribution, therapeutic efficacy, dosimetry, and safety were systematically assessed in prostate cancer xenograft models, with comparisons to radiolabeled antibody, ADC monotherapy, sequential therapy, and vehicle controls.<h4>Results</h4>Histological analysis in prostate cancer patients suggested B7-H3 was consistently and highly expressed in primary and metastatic lesions and remained stable under therapeutic intervention. The gene discussed is CD276; the disease is Familial prostate cancer.