Experimental research on the treatment of prostate cancer with the combination of 177Lu-PSMA-I&T and fluzoparib
10.3760/cma.j.cn321828-20240514-00168
- VernacularTitle:177Lu－PSMA－I&T联合氟唑帕利治疗前列腺癌的实验研究
- Author:
Bo LUO
1
;
Jiang WU
;
Pengjun ZHANG
;
Yutong XU
;
Zhengguo CHEN
;
Zhiyang WU
;
Feng WANG
;
Yong YANG
Author Information
1. 中国药科大学新药安全评价研究中心、基础医学与临床药学学院，南京 211198
- Publication Type:Journal Article
- Keywords:
Prostate-specific membrane antigen;
Isotope labeling;
Lutetium;
Urea;
Phthalazines;
Mice, nude
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(5):288-293
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of 177Lu-prostate specific membrane antigen (PSMA)-I&T combined with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor (PARPi) fluzoparib on the proliferation and migration of prostate cancer cells and the tumor inhibitory effects. Methods:177Lu-PSMA-I&T was synthesized. Cytotoxicity assay, colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay, Transwell cell migration assay, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, flow cytometry were performed to detect apoptosis and cell cycles. 22RV1 tumor-bearing mice models ( n=16) were established, and were randomly divided into 4 groups: control group (no treatment; n=4), fluzoparib monotherapy group (6mg/kg; n=4), 177Lu-PSMA-I&T monotherapy group (14.8MBq; n=4) and combination group (14.8MBq 177Lu-PSMA-I&T+ 6mg/kg fluzoparib; n=4). All mice were treated for 14 d. Tumor volume and body mass changes of tumor-bearing mice were observed and recorded. After the treatment, 18F-FDG PET/CT was performed to evaluate the tumor′s uptake of 18F-FDG. Effects of 177Lu-PSMA-I&T combined with fluzoparib on cell and tumor-bearing mice were observed. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:At half maximal inhibitory concentrations (IC 50) of 177Lu-PSMA-I&T (13.06MBq/ml) and fluzoparib (72.13μmol/L), compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment significantly enhanced the anti-tumor effect on 22RV1 cells, inhibited the DNA synthesis rate and colony-forming ability of 22RV1 cells, reduced cell migration rate, increased the percentage of DNA damage, resulted in a higher proportion of cells arrested in the G2/M phase and increased the apoptosis rate ( F values: 9.77-162.20, t values: 2.98-21.60, all P<0.05). Compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment resulted in a significant reduction in relative tumor volume (RTV%) 14 d post-administration and markedly decreased 18F-FDG uptake ( F values: 25.28 and 67.42, t values: 4.64-8.61, P values: 0.001-0.009). Conclusion:The combination of 177Lu-PSMA-I&T and fluzoparib can inhibit prostate cancer cell proliferation and migration, suppress tumor growth and metabolism, and demonstrates synergistic effects more effectively.
