Integrated radio-theranostics using a [ ⁸⁹ Zr]Zr-/[ ¹⁷⁷ Lu]Lu-labeled B7-H3 antibody-drug conjugate for prostate cancer

Rationale: Prostate cancer remains a leading cause of cancer-related mortality in men. Although PSMA-directed theranostics have achieved clinical success, heterogeneous expression and therapy-induced downregulation limit their broad applicability. B7-H3 (CD276), which is highly and stably expressed in prostate cancer, represents a promising alternative theranostic target. Methods: 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. Results: Lu]Lu administration were reversible. Conclusions: Lu]Lu-B7-H3 ADC theranostic platform enables accurate imaging, precise tumor targeting, and enhanced antitumor efficacy at reduced ADC doses without increasing systemic toxicity, supporting its translational potential for prostate cancer.