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188Re-(DXR)-脂质体-BBN 在 AR42J 胰腺荷瘤小鼠中的分子成像和治疗效果。

Molecular imaging and therapeutic efficacy of 188Re-(DXR)-liposome-BBN in AR42J pancreatic tumor-bearing mice.

机构信息

Institute of Nuclear Energy Research, No. 1000 Wenhua Rd., Jiaan Village, Longtan Township, Taoyuan County 32546, Taiwan, ROC.

出版信息

Oncol Rep. 2012 Nov;28(5):1736-42. doi: 10.3892/or.2012.1978. Epub 2012 Aug 22.

Abstract

Liposomes are good candidates as drug carriers and have been widely investigated in drug delivery systems. In this study, a new combination of bimodal 188Re-(DXR)-liposome-BBN radiochemotherapeutics was designed and studied for treating solid pancreatic tumor by intravenous administration. The in vivo nuclear microSPECT/CT imaging of tumor targeting, prolonged survival time and therapeutic efficacy were evaluated in AR42J malignant pancreatic solid tumor-bearing nude mice. MicroSPECT/CT imaging of 188Re-liposome-BBN pointed to significant targeting in tumors at 24 h after intravenous injection (SUV=2.13 ± 0.98). Co-injection of a blocking dose of cold BBN (4 mg/kg) inhibited the accumulation of 188Re-liposome-BBN in tumors (SUV=1.82 ± 0.31). For therapeutic efficacy, inhibition of tumor growth in mice treated with 188Re-DXR-liposome-BBN was precisely controlled [mean growth inhibition rate (MGI) = 0.092] and had longer survival time [life-span (LS) = 86.96%] than those treated with anticancer drug 188Re-liposome-BBN (MGI = 0.130; LS = 75%), Lipo-Dox-BBN (MGI = 0.666; LS = 3.61%) and untreated control mice. An additive tumor regression effect was observed (CI 0.946) for co-delivery of 188Re-DXR-liposome-BBN radiochemotherapeutics. These results point to the potential benefit of the 188Re-(DXR)-liposome-BBN radiochemotherapeutics for adjuvant cancer treatment with applications in oncology.

摘要

脂质体是药物载体的良好候选物,已在药物传递系统中得到广泛研究。在这项研究中,设计并研究了一种新的双模态 188Re-(DXR)-脂质体-BBN 放化疗联合药物,通过静脉给药治疗实体胰腺肿瘤。在 AR42J 恶性胰腺实体瘤荷瘤裸鼠中,通过体内核微 SPECT/CT 成像评估肿瘤靶向、延长生存时间和治疗效果。188Re-脂质体-BBN 的微 SPECT/CT 成像表明,静脉注射后 24 小时肿瘤具有明显的靶向性(SUV=2.13±0.98)。共注射冷 BBN(4mg/kg)阻断剂量可抑制 188Re-脂质体-BBN 在肿瘤中的积累(SUV=1.82±0.31)。对于治疗效果,用 188Re-DXR-脂质体-BBN 治疗的小鼠肿瘤生长抑制精确控制[平均生长抑制率(MGI)=0.092],且生存时间更长[寿命(LS)=86.96%],比用抗癌药物 188Re-脂质体-BBN(MGI=0.130;LS=75%)、Lipo-Dox-BBN(MGI=0.666;LS=3.61%)和未治疗对照组的小鼠效果更好。观察到 188Re-DXR-脂质体-BBN 放化疗联合药物共递送的肿瘤消退效果具有附加作用(CI 0.946)。这些结果表明,188Re-(DXR)-脂质体-BBN 放化疗联合药物在肿瘤学中的应用具有辅助癌症治疗的潜在益处。

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