Synthesis of 177Lu-labeled liquid metal-based ROS radiosensitizer and preliminary study of its therapeutic efficacy on breast cancer in mice
10.3760/cma.j.cn321828-20240229-00078
- VernacularTitle:177Lu－液态金属ROS放疗增敏剂的合成及对小鼠乳腺癌疗效的初步研究
- Author:
Junjie YAN
1
;
Chen SU
;
Jianhan LIN
;
Xinyu WANG
;
Donghui PAN
;
Yuping XU
;
Lizhen WANG
;
Chongyang CHEN
;
Min YANG
Author Information
1. 国家卫生健康委员会核医学重点实验室、江苏省分子核医学重点实验室、江苏省原子医学研究所，无锡 214063
- Keywords:
Breast neoplasms;
Isotope labeling;
Lutetium;
Radiotherapy;
Reactive oxygen species;
Tumor cells, cultured;
Mice, nude;
Optical imaging
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2024;44(6):343-348
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.
