Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of <sup>188</sup>Re-N,N-bis (2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) (<sup>188</sup>Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of <sup>188</sup>Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of <sup>188</sup>Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of <sup>188</sup>Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of <sup>188</sup>Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of <sup>188</sup>Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of <sup>188</sup>Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of <sup>188</sup>Re-liposome and the synergistic effect of the combination radiochemotherapeutics of <sup>188</sup>Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of nanoliposome radiochemotherapeutics for adjuvant cancer treatment on oncology applications.
Date:
2010-01
Relation:
Nuclear Medicine and Biology. 2010 Jan;37(1):95-104.
