Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging.

Details

Serval ID
serval:BIB_87D2648EE778
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging.
Journal
Journal of controlled release
Author(s)
Fuchs K., Kiss A., Bize P.E., Duran R., Denys A., Hopfgartner G., Borchard G., Jordan O.
ISSN
1873-4995 (Electronic)
ISSN-L
0168-3659
Publication state
Published
Issued date
10/01/2018
Peer-reviewed
Oui
Volume
269
Pages
128-135
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
This study describes the use of fluorescence imaging and mass spectrometry imaging, for imaging the anti-angiogenic drug sunitinib, used to treat liver cancer. These techniques allowed for the assessment of local delivery of the unlabeled therapeutic drug. More specifically, the spatial distribution of the drug and its metabolites after local administration was investigated, and drug levels in tumor and liver tissue over time were quantified. For this purpose, sunitinib-eluting microspheres were locoregionally injected into the tumor feeding arteries of rabbits bearing liver tumors. In adjacent areas of tumor and non-targeted contralateral liver tissue, sunitinib distribution was mapped around beads in occluded vessels 7, 12, 13 and 14days after embolization by means of the two imaging methods. Presence of sunitinib metabolites was assessed by mass spectrometry imaging. Sunitinib was found around microspheres in the tumor at day 7, 12, and 13. The drug was retained by the necrotic tumor tissue, resulting in homogeneously distributed and high levels of up to 40μg/g tissue in a 1.5mm radius around the beads. The drug was almost completely eliminated from the contralateral liver tissue. Several of the drug's metabolites, including its primary active metabolite SU12662, were detected in the tumor tissue over 13days. Sunitinib diffused from the beads and was retained at high, therapeutic levels during 13days. This was confirmed independently by complementary fluorescence and mass spectrometry imaging, which served as tools to confirm effective drug delivery after hepatic transarterial administration in situ. Compound: Sunitinib: PubChem CID 5329102.
Keywords
Angiogenesis Inhibitors/administration & dosage, Angiogenesis Inhibitors/pharmacokinetics, Animals, Cell Line, Tumor, Disease Models, Animal, Drug Delivery Systems, Liver/metabolism, Liver Neoplasms/metabolism, Mass Spectrometry, Microspheres, Optical Imaging, Rabbits, Sunitinib/administration & dosage, Sunitinib/pharmacokinetics, Biodistribution, Drug-eluting beads, Fluorescence imaging, MALDI-SRM mass spectrometry imaging, Sunitinib, Transarterial chemoembolization
Pubmed
Web of science
Create date
16/11/2017 18:07
Last modification date
20/08/2019 15:47
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