Abstract
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Objectives The aim of this study was to investigate the distribution, dosimetry and comparative efficacy of intravenously administrated 188Re-liposome and 5-FU in the CT26-luc lung-metastatic model.
Methods These studies were performed on mice at 25 d after tumor inoculation. The efficacy of 188Re-liposome (29.6 MBq) was compared with 5-FU (144 mg/kg), liposome and normal saline by a single-dose treatment in lung-metastatic tumor-bearing mice. Furthermore, the survival and dosimetry of mice after treatment were evaluated.
Results After intravenous administration of the 188Re-liposome, the levels of radioactivity in tumor were maintained at steady levels (from 5.40 to 5.67%ID/g) after 4 h to 24 h. In pharmacokinetics, the AUC(o→∞), MRT(o→∞) and Cl of 188Re-liposome in blood via intravenous route were 998 h*%ID/g, 28.7 h and 0.1 g/h, respectively. The excretion study of intravenously administrated 188Re-liposome was determined in feces and urine of CT26-luc lung-metastatic mice. The excreted fractions of feces and urine were 0.61 and 0.26, respectively. In dosimetry study, tissue-absorbed dose for 188Re-liposome in the liver and red marrow were 0.31 mGy/MBq and 0.08 mGy/MBq, respectively. Tumor-absorbed doses for the 188Re-liposome were 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after 188Re-liposome, 5-FU or normal saline treatments were evaluated. Consequently, radiotherapeutics of 188Re-liposome attained better life span (increase 34.9%; P = 0.005) of mice than that of normal saline group. The increase in life span of 188Re-liposome group was 2.5-fold than that of 5-FU group.
Conclusions These results indicate that intravenous administration of 188Re-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications