Localization of sunitinib in in vivo animal and in vitro experimental models by MALDI mass spectrometry imaging

被引:0
作者
James J. Connell
Yutaka Sugihara
Szilvia Török
Balázs Döme
József Tóvári
Thomas E. Fehniger
György Marko-Varga
Ákos Végvári
机构
[1] Lund University,Clinical Protein Science & Imaging, Department of Biomedical Engineering
[2] Lund University and Skåne University Hospital,Department of Oncology, Clinical Sciences
[3] National Korányi Institute of Pulmonology,Department of Thoracic Surgery
[4] Medical University of Vienna,Department of Thoracic Surgery
[5] Semmelweis University-National Institute of Oncology,Department of Biomedical Imaging and Image
[6] Medical University of Vienna,guided Therapy
[7] National Institute of Oncology,Department of Experimental Pharmacology
[8] Lund University,Center of Excellence in Biological and Medical Mass Spectrometry
[9] Tokyo Medical University,First Department of Surgery
[10] Lund University,CREATE Health
[11] Dublin Institute of Technology,Biomedical Science
来源
Analytical and Bioanalytical Chemistry | 2015年 / 407卷
关键词
Mass spectrometry; MALDI; MALDI-MSI; In vivo models; Drug; Sunitinib; Colorectal adenocarcinoma;
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摘要
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.
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页码:2245 / 2253
页数:8
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