Comparative Therapeutic Efficacy of Rhenium-188 Radiolabeled-Liposome and 5-Fluorouracil in LS-174T Human Colon Carcinoma Solid Tumor Xenografts

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome (Re-188-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of Re-188-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of Re-188-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of Re-188-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of Re-188-liposome using the Pearson's correlation analysis (r = 0.997). Pharmacokinetics of Re-188-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 Re-188-liposome (80% maximum tolerated dose [MTD], 23.7MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144mg/kg). The median survival time for mice treated with Re-188-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 Re-188-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 Re-188-liposome. The therapeutic efficacy of radiotherapeutics of Re-188-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.