Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States.
Mol Pharm. 2012 Sep 4;9(9):2513-22. doi: 10.1021/mp300132f. Epub 2012 Aug 23.
Most diagnosed early stage breast cancer cases are treated by lumpectomy and adjuvant radiation therapy, which significantly decreases the locoregional recurrence but causes inevitable toxicity to normal tissue. By using a technique of preparing liposomes carrying technetium-99m ((99m)Tc), rhenium-186 ((186)Re), or rhenium-188 ((188)Re) radionuclides, as well as chemotherapeutic agents, or their combination, for cancer therapy with real time image-monitoring of pharmacokinetics and prediction of therapy effect, this study investigated the potential of a novel targeted focal radiotherapy with low systemic toxicity using radioactive immunoliposomes to treat both the surgical cavity and draining lymph nodes in a rat breast cancer xenograft positive surgical margin model. Immunoliposomes modified with either panitumumab (anti-EGFR) or bevacizumab (anti-VEGF) were remote loaded with (99m)Tc diagnostic radionuclide, and injected into the surgical cavity of female nude rats with positive margins postlumpectomy. Locoregional retention and systemic distribution of (99m)Tc-immunoliposomes were investigated by nuclear imaging, stereofluorescent microscopic imaging, and gamma counting. Histopathological examination of excised draining lymph nodes was performed. The locoregional retention of (99m)Tc-immunoliposomes in each animal was influenced by the physiological characteristics of the surgical site of individual animals. Panitumumab- and bevacizumab-liposome groups had higher intracavitary retention compared with the control liposome groups. Draining lymph node uptake was influenced by both the intracavitary radioactivity retention level and metastasis status. The panitumumab-liposome group had higher accumulation on the residual tumor surface and in the metastatic lymph nodes. Radioactive liposomes that were cleared from the cavity were metabolized quickly and accumulated at low levels in vital organs. Therapeutic radionuclide-carrying specifically targeted panitumumab- and bevacizumab-liposomes have increased potential compared to non-antibody targeted liposomes for postlumpectomy focal therapy to eradicate remaining breast cancer cells inside the cavity and draining lymph nodes with low systemic toxicity.
大多数早期诊断的乳腺癌病例采用肿块切除术和辅助放射治疗，这显著降低了局部区域复发率，但对正常组织造成不可避免的毒性。通过使用制备载锝-99m（Tc-99m）、铼-186（Re-186）或铼-188（Re-188）放射性核素以及化疗药物或其组合的脂质体技术，进行实时药代动力学图像监测和治疗效果预测的癌症治疗，本研究探讨了使用放射性免疫脂质体进行新型靶向局部放疗的潜力，以低全身毒性治疗乳腺癌肿瘤切除术后阳性切缘的大鼠模型的手术腔和引流淋巴结。用 panitumumab（抗 EGFR）或 bevacizumab（抗 VEGF）修饰的免疫脂质体远程加载 Tc-99m 诊断放射性核素，并在肿瘤切除术后切缘阳性的雌性裸鼠手术腔内注射。通过核成像、立体荧光显微镜成像和伽马计数研究（99m）Tc-免疫脂质体的局部区域保留和全身分布。对切除的引流淋巴结进行组织病理学检查。每个动物局部保留（99m）Tc-免疫脂质体受个体动物手术部位生理特征的影响。panitumumab 和 bevacizumab 脂质体组的腔内保留率高于对照组脂质体组。引流淋巴结摄取受腔内放射性保留水平和转移状态的影响。panitumumab 脂质体组在残留肿瘤表面和转移性淋巴结中有更高的积聚。从腔内清除的放射性脂质体迅速代谢并在重要器官中低水平积累。与非抗体靶向脂质体相比，载有治疗放射性核素的特异性靶向 panitumumab 和 bevacizumab 脂质体具有更大的潜力，可用于肿瘤切除术后的局部治疗，以消除腔内和引流淋巴结中残留的乳腺癌细胞，同时具有低全身毒性。
