A New Pharmacokinetic Model Describing the Biodistribution of Intravenously and Intratumorally Administered Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a GL261 Xenograft Glioblastoma Model
A New Pharmacokinetic Model Describing the Biodistribution of Intravenously and Intratumorally Administered Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a GL261 Xenograft Glioblastoma Model
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DOI：
10.2147/ijn.s254745
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发表时间：
2020-01-01
影响因子：
8
通讯作者：
Multhoff, Gabriele
中科院分区：
文献类型：
--
作者：
Klapproth, Alexander P.;Shevtsov, Maxim;Multhoff, Gabriele
背景：超顺磁性氧化铁纳米颗粒(SPION)在全身给药后已在肿瘤治疗中显示出多功能的应用。为了提高局部治疗(包括局部热疗)的治疗潜力，纳米粒子也可以在肿瘤内给予治疗。因此，建立可靠的药物动力学模型来预测两种临床相关给药途径的纳米粒分布是非常重要的。材料和方法：研究放射性标记的两种不同大小的SPION(130 nm和60 nm)在C57/B16小鼠皮下GL261胶质母细胞瘤中的分布。基于PET/CT的生物分布数据，建立了一个新的药代动力学模型，以更好地了解SPION在两种给药途径后的药代动力学。结果：经组织学证实的纳米粒子的PET图像分析表明，在肿瘤内注射后的所有时间点，放射性标记的纳米粒子都存在于胶质瘤部位(肝和脾中含量较低)。该数学模型证实了纳米粒子在体内72小时内的动态再分布，在100小时后达到平衡。静脉注射纳米粒子呈现不同的分布模式，粒子在所有器官(特别是肝和脾)快速滞留，随后缓慢释放。结论：该数学模型与来自肿瘤小鼠模型的实验数据吻合良好，表明该工具可用于预测SPION在体内的实时药代动力学特征。未来，计划将我们的模型应用于其他纳米颗粒配方，以更准确地描述它们在体内模型系统中的生物分布。
Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance.Materials and Methods: The biodistribution of SPIONs (of two different sizes - 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/B16 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes.Results: The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate.Conclusion: The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems.