Practical theoretic guidance for the design of tumor-targeting agents.
Practical theoretic guidance for the design of tumor-targeting agents.
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DOI：
10.1016/b978-0-12-396962-0.00010-0
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发表时间：
2012
影响因子：
--
通讯作者：
Rhoden, John J.
中科院分区：
文献类型：
--
作者：
Wittrup, K. Dane;Thurber, Greg M.;Schmidt, Michael M.;Rhoden, John J.
靶向剂药代动力学的理论分析提供了具体的指导方面所需的设计目标，如代理的大小，亲和力，和靶抗原。这些分析表明IgG大小的大分子构建体在全身清除和血管外渗之间表现出最有利的平衡，导致最大的肿瘤摄取。还提供了剂量和结合亲和力对肿瘤摄取和渗透的影响的定量预测。小鼠中异种移植肿瘤饱和所需的单次推注剂量可以根据抗原表达水平和代谢半衰期的知识来预测。高结合亲和力在肿瘤摄取中的作用可以概括为：对小肽至关重要，对抗体不太重要，对纳米颗粒可忽略不计。
Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half-life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and negligible for nanoparticles.