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

Abstract 

The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated ¹⁸⁸Re-N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (¹⁸⁸Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality ¹⁸⁸Re-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→∞) of ¹⁸⁸Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of ¹⁸⁸Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated ¹⁸⁸Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after ¹⁸⁸Re-DXR-liposome (22.2 MBq of ¹⁸⁸Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of ¹⁸⁸Re-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 radiotherapeutics of ¹⁸⁸Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel ¹⁸⁸Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications.

Keywords: Bimodality nanoliposome delivery, Micro-SPECT/CT, Radiochemotherapy, ¹⁸⁸Re