Institute of Nuclear Energy Research, Taoyuan, Taiwan, ROC.
Nucl Med Biol. 2010 Jan;37(1):95-104. doi: 10.1016/j.nucmedbio.2009.08.006. Epub 2009 Oct 3.
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 (188)Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ((188)Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of (188)Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of (188)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 (188)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 (188)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 (188)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 (188)Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome and the synergistic effect of the combination radiochemotherapeutics of (188)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.
纳米载体可以选择性地靶向癌症部位并携带有效载荷，从而提高诊断和治疗效果并降低毒性。本研究的目的是研究新型共递药（188）Re-N，N-双（2-巯基乙基）-N'，N'-二乙基亚乙基二胺（BMEDA）标记的聚乙二醇化阿霉素脂质体（DXR）（（188）Re-DXR-脂质体）在 C26 小鼠结肠腺癌实体瘤模型中的治疗效果。为了评估（188）Re-DXR-脂质体在 C26 荷瘤小鼠中的靶向性和定位，进行了生物分布、microSPECT/CT 成像和药代动力学研究。通过肿瘤生长抑制、生存比例和组织病理学苏木精-伊红染色评估（188）Re-DXR-脂质体的抗肿瘤作用。通过生物分布、药代动力学和体内核成像研究，证明了纳米脂质体递送（188）Re-DXR-脂质体的放射化疗的肿瘤靶向和定位。在治疗效果研究中，与接受（188）Re-脂质体放射治疗（MGI=0.134；60 天）和脂质体阿霉素化疗（MGI=0.413；38 天）的肿瘤相比，接受（188）Re-DXR-脂质体双模态放射化疗的荷瘤小鼠显示出更好的平均肿瘤生长抑制率（MGI）和更长的中位生存时间（MGI=0.048；74 天）。对于共递药（188）Re-DXR-脂质体，协同肿瘤消退效应观察到组合指数（CI）超过 1（CI=1.145）。接受放射化疗的 2 只（25%）小鼠在 120 天后完全治愈。在 C26 小鼠实体瘤动物模型中，（188）Re-脂质体放射治疗的疗效和共递药（188）Re-DXR-脂质体的协同作用得到了证实，这表明纳米脂质体放射化疗共递药在肿瘤学应用中辅助癌症治疗的潜在益处和前景。
