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Journal of Nuclear Medicine

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Research ArticleTheranostics

Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer

Johannes Czernin, Kyle Current, Christine E. Mona, Lea Nyiranshuti, Firas Hikmat, Caius G. Radu and Katharina Lückerath
Journal of Nuclear Medicine February 2021, 62 (2) 228-231; DOI: https://doi.org/10.2967/jnumed.120.246041
Johannes Czernin
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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Kyle Current
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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Christine E. Mona
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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Lea Nyiranshuti
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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Firas Hikmat
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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Caius G. Radu
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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Katharina Lückerath
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
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This article has a correction. Please see:

  • Erratum - March 01, 2021

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Abstract

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.

  • 225Ac-PSMA
  • immunotherapy
  • prostate cancer
  • PD-1
  • syngeneic mouse model

Footnotes

  • Guest Editor: Todd Peterson, Vanderbilt University.

  • Published online Jul. 9, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (2)
Journal of Nuclear Medicine
Vol. 62, Issue 2
February 1, 2021
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Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer
Johannes Czernin, Kyle Current, Christine E. Mona, Lea Nyiranshuti, Firas Hikmat, Caius G. Radu, Katharina Lückerath
Journal of Nuclear Medicine Feb 2021, 62 (2) 228-231; DOI: 10.2967/jnumed.120.246041

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Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer
Johannes Czernin, Kyle Current, Christine E. Mona, Lea Nyiranshuti, Firas Hikmat, Caius G. Radu, Katharina Lückerath
Journal of Nuclear Medicine Feb 2021, 62 (2) 228-231; DOI: 10.2967/jnumed.120.246041
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Keywords

  • 225Ac-PSMA
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