Center for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum Rechts Der Isar, Munich, Germany.
Institute of Radiation Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Munich, Germany.
Int J Nanomedicine. 2020 Jun 30;15:4677-4689. doi: 10.2147/IJN.S254745. eCollection 2020.
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.
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.
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.
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.
超顺磁氧化铁纳米颗粒（SPIONs）在全身给药后，在癌症治疗学中显示出多功能应用。为了提高局部治疗（包括聚焦热疗）的治疗潜力，也可以瘤内给予纳米颗粒。因此，开发一种可靠的药代动力学模型来预测两种临床相关给药途径的纳米颗粒分布对于提高治疗效果具有重要意义。
用放射性核素锆-89 或锝-99m 标记两种不同大小（130nm 和 60nm）的 SPIONs，通过瘤内或静脉注射，研究其在皮下 GL261 胶质母细胞瘤荷瘤 C57/Bl6 小鼠中的生物分布。基于 PET/CT 生物分布数据，建立了一种新的药代动力学模型，以更好地理解两种给药途径后 SPIONs 的药代动力学。
纳米颗粒的 PET 图像分析（通过组织学证实）表明，在瘤内注射后所有研究时间点，放射性标记的纳米颗粒都存在于神经胶质瘤部位（肝脏和脾脏中的含量较低）。数学模型证实，纳米颗粒在体内会在 72 小时内发生动态再分布，在 100 小时后达到平衡。静脉注射纳米颗粒后，表现出不同的分布模式，所有器官（尤其是肝脏和脾脏）中粒子迅速滞留，随后释放速度缓慢。
数学模型与肿瘤小鼠模型的实验数据具有良好的一致性，表明该工具可用于预测 SPIONs 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制剂，以更精确地描述它们在体内模型系统中的生物分布。
