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

被引:12
作者
Connell, James J. [1 ]
Sugihara, Yutaka [2 ,3 ]
Torok, Szilvia [4 ]
Doeme, Balazs [4 ,5 ,6 ]
Tovari, Jozsef [7 ]
Fehniger, Thomas E. [1 ,8 ]
Marko-Varga, Gyorgy [1 ,8 ,9 ]
Vegvari, Akos [1 ,10 ]
机构
[1] Lund Univ, Dept Biomed Engn, Clin Prot Sci & Imaging, S-22184 Lund, Sweden
[2] Lund Univ, Dept Oncol, Clin Sci, S-22185 Lund, Sweden
[3] Skane Univ Hosp, S-22185 Lund, Sweden
[4] Natl Koranyi Inst Pulmonol, H-1121 Budapest, Hungary
[5] Semmelweis Univ, Natl Inst Oncol, Dept Thorac Surg, H-1122 Budapest, Hungary
[6] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, A-1090 Vienna, Austria
[7] Natl Inst Oncol, Dept Expt Pharmacol, H-1122 Budapest, Hungary
[8] Lund Univ, Ctr Excellence Biol & Med Mass Spectrometry, S-22184 Lund, Sweden
[9] Tokyo Med Univ, Dept Surg 1, Shinjuku Ku, Tokyo 1600023, Japan
[10] Lund Univ, CREATE Hlth, S-22100 Lund, Sweden
基金
瑞典研究理事会;
关键词
Mass spectrometry; MALDI; MALDI-MSI; In vivo models; Drug; Sunitinib; Colorectal adenocarcinoma; METASTATIC COLORECTAL-CANCER; ASSISTED-LASER-DESORPTION/IONIZATION; DRUG DISTRIBUTIONS; BRAIN-TISSUE; PHASE-II; NORMALIZATION; FLUOROURACIL; LEUCOVORIN; IRINOTECAN; PHARMACOKINETICS;
D O I
10.1007/s00216-014-8350-2
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:2245 / 2253
页数:9
相关论文
共 41 条
[1]   Ion suppression in mass spectrometry [J].
Annesley, TM .
CLINICAL CHEMISTRY, 2003, 49 (07) :1041-1044
[2]   Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors [J].
Bergers, G ;
Song, S ;
Meyer-Morse, N ;
Bergsland, E ;
Hanahan, D .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (09) :1287-1295
[3]   Imaging mass spectrometry: Principles and potentials [J].
Chaurand, P ;
Schwartz, SA ;
Reyzer, ML ;
Caprioli, RA .
TOXICOLOGIC PATHOLOGY, 2005, 33 (01) :92-101
[4]   Normalization in MALDI-TOF imaging datasets of proteins: practical considerations [J].
Deininger, Soeren-Oliver ;
Cornett, Dale S. ;
Paape, Rainer ;
Becker, Michael ;
Pineau, Charles ;
Rauser, Sandra ;
Walch, Axel ;
Wolski, Eryk .
ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 2011, 401 (01) :167-181
[5]   Vascularization of cutaneous melanoma involves vessel co-option and has clinical significance [J].
Döme, B ;
Paku, S ;
Somlai, B ;
Tímár, J .
JOURNAL OF PATHOLOGY, 2002, 197 (03) :355-362
[6]   Metastatic colorectal cancer:: integrating irinotecan into combination and sequential chemotherapy [J].
Douillard, JY ;
Sobrero, A ;
Carnaghi, C ;
Comella, P ;
Díaz-Rubio, E ;
Santoro, A ;
Van Cutsem, E .
ANNALS OF ONCOLOGY, 2003, 14 :7-12
[7]   Lifestyle Modifications and Colorectal Cancer [J].
Durko, Lukasz ;
Malecka-Panas, Ewa .
CURRENT COLORECTAL CANCER REPORTS, 2014, 10 (01) :45-54
[8]   Combined inhibition of VEGF- and PDGF-signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms [J].
Erber, R ;
Thurnher, A ;
Katsen, AD ;
Groth, G ;
Kerger, H ;
Hammes, HP ;
Menger, MD ;
Ullrich, A ;
Vajkoczy, P .
FASEB JOURNAL, 2003, 17 (15) :338-340
[9]   Direct Demonstration of Tissue Uptake of an Inhaled Drug: Proof-of-Principle Study Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging [J].
Fehniger, Thomas E. ;
Vegvari, Akos ;
Rezeli, Melinda ;
Prikk, Kaiu ;
Ross, Peeter ;
Dahlback, Magnus ;
Edula, Goutham ;
Sepper, Ruth ;
Marko-Varga, Gyorgy .
ANALYTICAL CHEMISTRY, 2011, 83 (21) :8329-8336
[10]   MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals [J].
Fujimura, Yoshinori ;
Miura, Daisuke .
METABOLITES, 2014, 4 (02) :319-346