Fluorination augments tumor engagement and antitumor immunity of a D-peptide-based radiotheranostic agent for combinatorial immune checkpoint blockade therapy

BACKGROUND: Cu]DPA, which exhibited favorable in vivo stability. Nevertheless, its inadequate tumor retention hampers therapeutic efficacy and immune activation, highlighting the need for further optimization to achieve sustained target engagement. METHODS: Lu-labeled fluorinated radiopharmaceuticals was further investigated to verify their potential in enhancing antitumor immunity. RESULTS: Lu]D3-6 boosted both local and systemic antitumor immunity and, in combination with anti-programmed cell death protein-1 therapy, elicited superior tumor inhibition. CONCLUSION: This study highlights the potential of fluorinated D-peptide radiopharmaceuticals as powerful PD-L1 targeting radiotheranostics, enabling more effective systemic antitumor efficacy in RPT and ICB combination therapy.