MicroSPECT/CT imaging and therapeutic efficacy of 188Re-liposomes and 5-FU in LS-174T human colon carcinoma solid tumor xenografts

Objectives This study was to investigate the distribution, imaging and therapeutic efficacy of 188Re-Liposome and 5-FU in murine LS-174T human colon adenocarcinoma-bearing nude mice by i.v. injection.

Methods To evaluate the targeting and localization of 188Re-Liposome in LS-174T human tumor-bearing mice, the biodistribution, microSPECT/CT imaging, whole-body autoradiography image and pharmacokinetics studies were performed. The tumor effect of 188Re-Liposome was assessed by tumor growth inhibition, survival ration.

Results The MTD of 188Re-Liposome and 5-FU were 29.6 MBq and 180 mg/kg, respectively. For the biodistribution study, the highest uptake in LS-174T tumor was found to be 11.27% ± 0.99% at 24 h, and the tumor to muscle ratio of 188Re-Liposome was 16.07% ± 1.91%. MicroSPECT/CT imaging indicated the highest uptake of 188Re-liposome at 24, 48, and 72 h after injection. The imaging analysis showed a positive correlation of tumor targeting of 188Re-liposome between biodistribution and microSPECT/CT imaging. For therapeutic efficacy, the large tumor-bearing mice (~300 mm3) treated with 188Re-Liposome (23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (144 mg/kg). The median survival times for mice treated with 188Re-Liposome (53.78 days; P<.05) and 5-FU (43.17 days; P>.05) were better than those from normal saline treated mice (25.88 days).

Conclusions The results of the in vivo nuclear imaging studies revealed the potential advantage and benefit of our developed 188Re-Liposome for site-specific tumor imaging and therapeutics. The therapeutic efficacy of radio-therapeutics of 188Re-Liposome have been confirmed in a LS-174T solid tumor animal model, which pointed to the potential benefit and promise of the passive nanoliposome delivery radio-therapeutics for cancer treatment on oncology applications