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Localization of sunitinib, its metabolites and its target receptors in tumor bearing mice: a MALDI mass spectrometry imaging study
- Török, Szilvia (author)
-
- Végvári, Ákos (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Rezeli, Melinda (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Tóvári, József (author)
- Paku, Sándor (author)
- László, Viktória (author)
- Hegedüs, Balázs (author)
- Rózsás, Anita (author)
- Döme, Balázs (author)
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- (creator_code:org_t)
- 2015-01-12
- 2015
- English.
- In: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 172:4, s. 1148-1163
- Journal article (peer-reviewed)
Abstract
Subject headings
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- A functional blood vessel network is essential for maintaining the necessary oxygen and nutrient levels in solid tumors. Thus, the inhibition of blood vessel growth by different antiangiogenic agents has become one of the most important topics in cancer research over the past few decades. The in vitro studies of these drugs are promising, but both the in vivo and the clinical experiences are controversial. Therefore, investigating the pharmacokinetic parameters of these compounds is a pivotal issue in drug development. In this study, the detection and the adsorption, distribution, metabolism, elimination (ADME) of the antiangiogenic receptor tyrosine kinase inhibitor (RTKI) sunitinib is analyzed in a subcutaneous syngeneic murine tumor model of colorectal cancer. The parent molecule of sunitinib was detected at m/z 399.218 with fragment ions at m/z 326.1 and 283.1 with matrix assisted laser desorption ionization (MALDI) technique. Metabolites of the drug were measured in blood samples and main metabolites were found in tumor, liver and kidney tissues at m/z 371.188, 397.203 and 415.214. Tissue distribution of the drug and its metabolites showed an overlapping pattern by MALDI imaging. The present study supports the role of the MALDI technique in the ADME characterization of drug candidates in preclinical drug development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- sunitinib
- MALDI
- imaging
- mass spectrometry
- angiogenesis
- RTKI
Publication and Content Type
- art (subject category)
- ref (subject category)
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- Török, Szilvia
- Végvári, Ákos
- Rezeli, Melinda
- Fehniger, Thomas
- Tóvári, József
- Paku, Sándor
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- László, Viktória
- Hegedüs, Balázs
- Rózsás, Anita
- Döme, Balázs
- Marko-Varga, Gyö ...
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