RT Journal Article SR Electronic T1 Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 228 OP 231 DO 10.2967/jnumed.120.246041 VO 62 IS 2 A1 Johannes Czernin A1 Kyle Current A1 Christine E. Mona A1 Lea Nyiranshuti A1 Firas Hikmat A1 Caius G. Radu A1 Katharina Lückerath YR 2021 UL http://jnm.snmjournals.org/content/62/2/228.abstract AB Prostate-specific membrane antigen (PSMA)–targeted radionuclide therapy (RNT) may increase tumor immunogenicity. We aimed at exploiting this effect by combining RNT with immunotherapy in a mouse model of prostate cancer (PC). Methods: C57BL/6-mice bearing syngeneic RM1-PGLS tumors were treated with 225Ac-PSMA617, an anti-PD-1 antibody, or both. Therapeutic efficacy was assessed by tumor volume measurements (CT), time to progression (TTP), and survival. Results: PSMA RNT or anti-PD-1 alone tended to prolong TTP (isotype control, 25 d; anti-PD-1, 33.5 d [P = 0.0153]; RNT, 30 d [P = 0.1038]) and survival (control, 28 d; anti-PD-1, 37 d [P = 0.0098]; RNT, 32 d [P = 0.1018]). Combining PSMA RNT and anti-PD-1 significantly improved disease control compared with either monotherapy. TTP was extended to 47.5 d (P ≤ 0.0199 vs. monotherapies), and survival to 51.5 d (P ≤ 0.0251 vs. monotherapies). Conclusion: PSMA RNT and PD-1 blockade synergistically improve therapeutic outcomes in our PC model, supporting the evaluation of RNT and immunotherapy combinations for PC patients.