Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, Texas, USA.
Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, New Mexico, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020 Sep;12(5):e1628. doi: 10.1002/wnan.1628. Epub 2020 Apr 21.
While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug-loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size-dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non-invasive in vivo imaging modalities. This allows for visualization and quantification of the whole-body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non-invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state-of-the-art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
虽然血浆浓度动力学一直是预测药物药效学的指标，但它偶尔无法代表作用部位的动力学，特别是对于实体瘤。对于治疗性大分子（载药纳米材料或单克隆抗体）的输送尤其如此，由于目标部位的粒径依赖性扩散障碍，它们可能会遇到有效输送的挑战。因此，治疗性血浆动力学和作用部位动力学之间可能存在差异，这凸显了确定大分子治疗剂药效学的靶部位浓度动力学的重要性。非侵入性体内成像技术促进了靶部位浓度动力学的评估。这使得对治疗剂的全身处置行为进行可视化和量化成为可能，这对于全面了解其药代动力学和药效学至关重要。定量非侵入性成像还可以帮助指导数学模型的开发和参数化，以进行描述性和预测性目的。在这里，我们综述了最先进的成像技术在治疗性纳米颗粒和单克隆抗体的定量药理学评估中的应用，重点介绍了它们与数学模型的整合，并确定了挑战和机遇。本文属于以下类别：治疗方法和药物发现 > 用于肿瘤疾病的纳米医学诊断工具 > 体内纳米诊断和成像 生物学中的纳米技术方法 > 生物学中的纳米级系统。
