Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome (188Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of 188Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of 188Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of 188Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of 188Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of 188Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with 188Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with 188Re-liposome (58.5 days; p<0.05) was significantly better than those of 5-FU (48.25 days; p>0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the 188Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of 188Re-liposome. The therapeutic efficacy of radiotherapeutics of 188Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.
Date:
2012-10-15
Relation:
Cancer Biotherapy and Radiopharmaceuticals. 2012 Oct 15;27(8):481-489.
