Citation: Hong Wang, Zhenwen Zhao, Xiao Xu, Zhide Guo, Gang Liu. Ultra-low-dose radioimmunotherapy improves prostate cancer treatment efficacy and safety[J]. Chinese Chemical Letters, ;2026, 37(8): 111799. doi: 10.1016/j.cclet.2025.111799 shu

Ultra-low-dose radioimmunotherapy improves prostate cancer treatment efficacy and safety

Hong Wang ^{a, 1} ,
Zhenwen Zhao ^{a, 1} ,
Xiao Xu ^{b, c, *,} ,
Zhide Guo ^{a, *,} ,
Gang Liu ^{a, *,}

a.
State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen 361102, China
b.
Cancer Center, Dongguan Engineering Research Center for Innovative Boron Drugs and Novel Radioimmune Drugs, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523059, China
c.
Guangdong Engineering Research Center of Boron Neutron Therapy and Application in Malignant Tumors, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523059, China

xiaoxu721@smu.edu.cn

gzd666888@xmu.edu.cn

gangliu.cmitm@xmu.edu.cn

Received Date: 17 December 2024
Revised Date: 5 September 2025
Accepted Date: 7 September 2025
Available Online: 8 September 2025

Figures(4)

Prostate cancer poses a severe threat to the health of middle-aged and elderly males. In recent years, the development and clinical utilization of prostate-specific membrane antigen (PSMA)-targeted agents have significantly expanded diagnostic options for this malignancy. However, tumor heterogeneity substantially compromises the efficacy of radionuclide therapy, necessitating the exploration of multi-target strategies as potential solutions. This study presents a novel heterodimeric construct engineered for prostate cancer management, labeled with both diagnostic and therapeutic radionuclides to enable concurrent application in positron emission computed tomography (PET) imaging and radionuclide therapy. Our investigation primarily evaluates the therapeutic efficacy of ultra-low-dose (3.7 MBq) radionuclide therapy combined with anti-programmed cell death protein-1 (PD-1) antibody immunotherapy. In the RM-1 prostate cancer model with elevated PSMA expression, we have validated that the combination of ultra-low-dose radionuclide treatment and anti-PD-1 antibody immunotherapy yields superior therapeutic outcomes. Notably, compared to the immunotherapy-only group, the combination regimen elicited a significant increase in dendritic cells (DCs) and natural killer (NK) cells populations, with enhancements ranging from 32% to 103%. This ultra-low-dose radioimmunotherapy strategy offers a valuable theoretical framework for clinical translation, holding promise for further enhancing therapeutic efficacy in prostate cancer treatment.
- PSMA,
- GRPR,
- Theranostics,
- Tumor heterogeneity,
- Ultra-low-dose radioimmunotherapy
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