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首页> 外文期刊>International Journal of Nanomedicine >Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model
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Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

机译：188Re标记的聚乙二醇化纳米脂质体作为放射性核素治疗剂在原位神经胶质瘤大鼠模型中的评价

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Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome) was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc) showed a high relationship between cell number and its bioluminescent intensity (R2=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with 188Re-liposome was prolonged 10.67% compared to the control group.Conclusion: The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, 188Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.
机译：目的：本研究制备了188Re标记的聚乙二醇化纳米脂质体（188Re-脂质体），并作为胶质瘤的治疗药物进行了评价。材料与方法：通过Lentivector表达试剂盒系统制备报告细胞F98luc，并用于建立原位神经胶质瘤大鼠模型进行非侵入性生物发光成像。在治疗研究之前，通过单剂量静脉内注射188Re-脂质体后，通过监测大鼠的体重，探索了适用于Fischer344大鼠的最大耐受剂量。使用OLINDA / EXM 1.1软件估算辐射剂量。为了评估治疗效果，给荷瘤大鼠静脉内注射188Re-脂质体或生理盐水，然后监测肿瘤生长和动物存活时间。此外，还对188Re-脂质体处理的大鼠进行了肿瘤组织病理学检查。结果：通过生物发光成像，成熟的报告细胞（F98luc）显示出细胞数量与其生物发光强度（R2 = 0.99）;此外，它还可以提供清晰的肿瘤影像，以监测体内肿瘤的生长。 Fischer344大鼠中188Re-脂质体的最大耐受剂量估计为333 MBq。根据剂量测定结果，在脾脏和肾脏中观察到更高的当量剂量，而在正常的大脑，红骨髓和甲状腺中观察到的当量剂量则更少。为了进行疗效研究，188Re-脂质体治疗组的肿瘤生长（以肿瘤体积和/或肿瘤重量计）比对照组明显更慢（P <0.05）。结果，与对照组相比，接受188Re-脂质体治疗的神经胶质瘤大鼠的寿命延长了10.67％。结论：剂量学和生存研究的放射治疗评估表明，通过全身给药被动靶向188Re-脂质体可以显着延长维持原位神经胶质瘤大鼠的寿命，同时保持合理的全身放射安全性。因此，188Re-脂质体可能是多形性胶质母细胞瘤治疗的潜在治疗剂。

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