Therapeutic efficacy and microSPECT/CT imaging of 188Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

被引:65
作者
Chang, Ya-Jen [1 ]
Chang, Chih-Hsien [1 ]
Yu, Chia-Yu [1 ]
Chang, Tsui-Jung [1 ]
Chen, Liang-Cheng [1 ]
Chen, Min-Hua [2 ]
Lee, Te-Wei [1 ]
Ting, Gann [2 ]
机构
[1] Inst Nucl Energy Res, Tao Yuan, Taiwan
[2] Natl Hlth Res Inst, Miaoli, Taiwan
关键词
Colon cancer; Combination therapy; Liposomal doxorubicin; Liposome; Micro-SPECT/CT; Radiochemotherapeutics; Rhenium-188; ANTITUMOR-ACTIVITY; DRUG-DELIVERY; PEGYLATED LIPOSOMES; COLORECTAL-CANCER; BREAST-CANCER; GROWTH-FACTOR; MOUSE MODEL; NUDE-MICE; PHARMACOKINETICS; BIODISTRIBUTION;
D O I
10.1016/j.nucmedbio.2009.08.006
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 Re-188-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) (Re-188-DXR-liposome) in a C26 marine colon carcinoma solid tumor model. To evaluate the targeting and localization of Re-188-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of Re-188-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 Re-188-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 Re-188-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 Re-188-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 Re-188-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of Re-188-liposome and the synergistic effect of the combination radiochemotherapeutics of Re-188-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. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:95 / 104
页数:10
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