Connell James J, Sugihara Yutaka, Török Szilvia, Döme Balázs, Tóvári József, Fehniger Thomas E, Marko-Varga György, Végvári Ákos
Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Biomedical Center D13, 221 84, Lund, Sweden.
Anal Bioanal Chem. 2015 Mar;407(8):2245-53. doi: 10.1007/s00216-014-8350-2. Epub 2014 Nov 26.
The spatial distribution of an anticancer drug and its intended target within a tumor plays a major role on determining how effective the drug can be at tackling the tumor. This study provides data regarding the lateral distribution of sunitinib, an oral antiangiogenic receptor tyrosine kinase inhibitor using an in vitro animal model as well as an in vitro experimental model that involved deposition of a solution of sunitinib onto tissue sections. All tumor sections were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging and compared with subsequent histology staining. Six tumors at four different time points after commencement of in vivo sunitinib treatment were examined to observe the patterns of drug uptake. The levels of sunitinib present in in vivo treated tumor sections increased continuously until day 7, but a decrease was observed at day 10. Furthermore, the in vitro experimental model was adjustable to produce a drug level similar to that obtained in the in vivo model experiments. The distribution of sunitinib in tissue sections treated in vitro appeared to agree with the histological structure of tumors, suggesting that this approach may be useful for testing drug update.
抗癌药物及其在肿瘤内的预期靶点的空间分布在决定药物对抗肿瘤的有效性方面起着主要作用。本研究提供了关于舒尼替尼横向分布的数据,舒尼替尼是一种口服抗血管生成受体酪氨酸激酶抑制剂,使用体外动物模型以及体外实验模型,该模型涉及将舒尼替尼溶液沉积到组织切片上。所有肿瘤切片均通过基质辅助激光解吸/电离质谱成像进行分析,并与随后的组织学染色进行比较。在体内舒尼替尼治疗开始后的四个不同时间点检查了六个肿瘤,以观察药物摄取模式。体内治疗的肿瘤切片中舒尼替尼的水平持续增加直至第7天,但在第10天观察到下降。此外,体外实验模型可进行调整,以产生与体内模型实验中获得的药物水平相似的药物水平。体外处理的组织切片中舒尼替尼的分布似乎与肿瘤的组织结构一致,这表明该方法可能有助于测试药物摄取。