The experimental study on intraperitoneal injection of targeted degradable nanoparticles 177Lu-FA-DOTA-PEG-PLGA in the treatment of ovarian cancer peritoneal metastases and ascites / 中华放射医学与防护杂志

ABSTRACT

Objective:To observe the distribution of 177Lu-FA-DOTA-PEG-PLGA nanoparticles in vivo, and evaluate the therapeutic effect of nanoparticles intraperitoneal injection on ovarian cancer peritoneal metastases and ascites. Methods:Nanoparticles were prepared and injected into human ovarian cancer xenograft nude mice model by tail vein. Micro-SPECT/CT imaging was performed at different times (4, 24, 72 h and 7 d) after injection to observe the distribution of nanoparticles in vivo. Nude mouse models of intraperitoneal metastases of human ovarian cancer were randomly divided into negative control group (normal saline), chemotherapy group (cisplatin 3 mg/kg, twice a week) and nanoparticle group (18.5 MBq), with 4 mice in each group. After 7 days, intraperitoneal tumor growth was evaluated by in vivo fluorescence imaging. The relative tumor inhibition rate was counted. Tumor cell apoptosis rate was detected by TUNEL method, and the proliferation activity tumor Ki67 was detected by immunohistochemical method. The ascites volume of each group was compared after treatment. Results:Micro-SPECT/CT imaging showed the radioactive uptake of the transplanted tumor, and the 24 h tumor muscle uptake ratio (T/M) was the highest, about 2.81±0.49. Intravital fluorescence imaging showed that, after intraperitoneal administration, the fluorescence intensity of abdominal tumor in particle group, chemotherapy group and control group was (1.45±0.19)×10 10, (2.21±0.36)×10 10 and (2.63±0.79)×10 10( F=6.09, P=0.029), respectively. The relative tumor growth inhibition (TGI) of the particle group and the chemotherapy group were 35.6% and 18.6%, respectively. The tumor cell apoptosis rates in particle group and chemotherapy group were higher than those in control group ( F=9.96, P=0.009). Ki67 indexes in particle group and chemotherapy group were lower than those in control group ( F=9.93, P=0.013). The ascites volume in particle group and chemotherapy group were both smaller than those in control group ( F=13.43, P=0.006). Conclusions:177Lu-FA-DOTA-PEG-PLGA nanoparticles can be used for the targeted imaging of ovarian cancer. After intraperitoneal injection, nanoparticles show local retention, degradation and absorption and thus inhibit the growth of peritoneal metastases and ascites of ovarian cancer, which provides a new idea for the diagnosis and treatment of advanced ovarian cancer with peritoneal metastasis.