Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of 188Re-DXR-liposome in C26 colon carcinoma ascites mice model

The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated Re-188-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated lipogomal doxorubicin (Re-188-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality Re-188-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o ->infinity)) of Re-188-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of Re-188-BMEDA, respectively. The maximum tolerated (lose of intraperitoneally administrated Re-188-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after Re-188-MR-liposome (22.2 MBq of Re-188, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of Re-188-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P<.05) in mice than radiochemotherapeutics of Re-188-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel Re-188-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications. (c) 2008 Elsevier Inc. All rights reserved.