Division of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan.
Department of Medical Oncology and Translational Research, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Sci Rep. 2020 Sep 23;10(1):15535. doi: 10.1038/s41598-020-72665-5.
Penetration of nanoparticles into viable tumor regions is essential for an effective response. Mass spectrometry imaging (MSI) is a novel method for evaluating the intratumoral pharmacokinetics (PK) of a drug in terms of spatial distribution. The application of MSI for analysis of nanomedicine PK remains in its infancy. In this study, we evaluated the applicability of MALDI-MSI for nanoparticle-formulated drug visualization in tumors and biopsies, with an aim toward future application in clinical nanomedicine research. We established an analytic method for the free drug (AZD2811) and then applied it to visualize nanoparticle-formulated AZD2811. MSI analysis demonstrated heterogeneous intratumoral drug distribution in three xenograft tumors. The intensity of MSI signals correlated well with total drug concentration in tumors, indicating that drug distribution can be monitored quantitatively. Analysis of tumor biopsies indicated that MSI is applicable for analyzing the distribution of nanoparticle-formulated drugs in tumor biopsies, suggesting clinical applicability.
纳米颗粒进入存活肿瘤区域对于有效反应至关重要。质谱成像 (MSI) 是一种评估药物在空间分布方面的肿瘤内药代动力学 (PK) 的新方法。MSI 在分析纳米医学 PK 中的应用仍处于起步阶段。在这项研究中，我们评估了 MALDI-MSI 在肿瘤和活检中用于可视化纳米颗粒制剂药物的适用性，以期在未来的临床纳米医学研究中应用。我们建立了一种用于游离药物 (AZD2811) 的分析方法，然后应用该方法可视化纳米颗粒制剂的 AZD2811。MSI 分析表明，三种异种移植肿瘤中存在异质性的肿瘤内药物分布。MSI 信号的强度与肿瘤中的总药物浓度很好地相关，表明可以定量监测药物分布。肿瘤活检分析表明，MSI 适用于分析肿瘤活检中纳米颗粒制剂药物的分布，表明具有临床适用性。
