Comparative therapeutic efficacy evaluation of 188Re-liposome and fluorouracil in C26 colonic peritoneal carcinomatosis mice model

Objectives This study was purposed to evaluate the therapeutic efficacy, biodistribution, pharmacokinetics, micro-SPECT/CT image, and dosimetry of 188Re-liposomes in the C26 colon carcinoma peritoneal metastasis mice model.

Methods Colon carcinoma peritoneal metastatic BALB/c mice were intravenously (i.v) administrated with 188Re-liposomes. For therapeutic efficacy, the survival, tumor and ascites inhibition of mice after treating with 188Re-liposomes and fluorouracil (5-FU) respectively were evaluated and compared. The biodistribution experiments and micro-SPECT/CT image were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA/EXM computer program was used for the dosimetry evaluation.

Results Radiochemotherapeutics of 188Re-liposome attained better survival time (increased by 34.6%; P<0.05), tumor and ascites inhibition (decreased by 63.4% and 83.2% at 7 days after treatment; P<0.05)than chemotherapeutics of 5-FU. In the bio-distribution study, the highest uptake of 188Re-liposomes was 7.91% ± 2.02% at 24h after i.v. administration and the high tumor/muscle ratio was observed. Micro-SPECT/CT image of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, feces, and tumor. Pharmacokinetics of 188Re-liposomes was showed the properties of high circulation time and high bioavailability (MRT=19.22h, AUC=820.39 %ID /g*h). Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue, but did in small tumor.

Conclusions These results demonstrated that the use of 188Re-liposomes for passively targeted tumor therapy exhibited greater therapeutic effects than the currently clinical applied chemotherapeutics drug 5-FU. The ideal pharmacological properties of 188Re-liposomes were showed in this study suggested the potential benefit and safety in treating peritoneal carcinomatasis of colon cancer