Localization of sunitinib, its metabolites and its target receptors in tumor bearing mice: a MALDI mass spectrometry imaging study
(2015) In British Journal of Pharmacology 172(4). p.1148-1163- Abstract
- 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... (More)
- 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. (Less)
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https://lup.lub.lu.se/record/4699047
- author
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- sunitinib, MALDI, imaging, mass spectrometry, angiogenesis, RTKI
- in
- British Journal of Pharmacology
- volume
- 172
- issue
- 4
- pages
- 1148 - 1163
- publisher
- Wiley
- external identifiers
-
- pmid:25363319
- wos:000348507700015
- scopus:84921667759
- pmid:25363319
- ISSN
- 1476-5381
- DOI
- 10.1111/bph.12990
- language
- English
- LU publication?
- yes
- id
- 60db3e98-3a29-48d9-a21e-750d03637244 (old id 4699047)
- date added to LUP
- 2016-04-01 13:19:27
- date last changed
- 2023-09-02 22:07:28
@article{60db3e98-3a29-48d9-a21e-750d03637244, abstract = {{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.}}, author = {{Török, Szilvia and Végvári, Ákos and Rezeli, Melinda and Fehniger, Thomas and Tóvári, József and Paku, Sándor and László, Viktória and Hegedüs, Balázs and Rózsás, Anita and Döme, Balázs and Marko-Varga, György}}, issn = {{1476-5381}}, keywords = {{sunitinib; MALDI; imaging; mass spectrometry; angiogenesis; RTKI}}, language = {{eng}}, number = {{4}}, pages = {{1148--1163}}, publisher = {{Wiley}}, series = {{British Journal of Pharmacology}}, title = {{Localization of sunitinib, its metabolites and its target receptors in tumor bearing mice: a MALDI mass spectrometry imaging study}}, url = {{http://dx.doi.org/10.1111/bph.12990}}, doi = {{10.1111/bph.12990}}, volume = {{172}}, year = {{2015}}, }