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/Bl6 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.



中文翻译：

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一种新的药代动力学模型，描述了 GL261 异种移植胶质母细胞瘤模型中静脉内和瘤内施用的超顺磁性氧化铁纳米颗粒 (SPION) 的生物分布。

背景：超顺磁性氧化铁纳米颗粒 (SPIONs) 在全身给药后已在癌症治疗学中显示出多功能应用。为了增加局部疗法（包括局部热疗）的治疗潜力，纳米颗粒也可以在肿瘤内给药。因此，开发用于预测两种临床相关递送途径的纳米颗粒分布的可靠药代动力学模型非常重要。
材料和方法：在带有皮下 GL261 胶质母细胞瘤的 C57/Bl6 小鼠中研究了在瘤内或静脉内注射后用锆 89 或锝 99m 放射性标记的 SPION（两种不同尺寸 - 130 nm 和 60 nm）的生物分布。基于 PET/CT 生物分布数据，建立了一种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：纳米颗粒的 PET 图像分析（通过组织学证实）表明，在肿瘤内注射后的所有研究时间点，神经胶质瘤部位（肝脏和脾脏中的数量很少）内存在放射性标记的纳米颗粒。数学模型证实了 72 小时内生物体内的动态纳米粒子再分布，100 小时后达到平衡。静脉注射纳米颗粒表现出不同的分布模式，所有器官（特别是肝脏和脾脏）中的颗粒快速保留，随后释放速度缓慢。
结论：该数学模型与来自肿瘤小鼠模型的实验数据表现出良好的一致性，表明该工具在预测体内 SPION 的实时药代动力学特征方面具有价值。未来，我们计划将我们的模型应用于其他纳米粒子配方，以更准确地描述它们在体内模型系统中的生物分布。