dc.contributor.author |
Bytzek, AK |
en |
dc.contributor.author |
Koellensperger, G |
en |
dc.contributor.author |
Keppler, BK |
en |
dc.contributor.author |
Hartinger, Christian |
en |
dc.date.accessioned |
2016-08-04T01:45:59Z |
en |
dc.date.issued |
2016-07 |
en |
dc.identifier.citation |
Journal of Inorganic Biochemistry, 2016, 160 pp. 250 - 255 |
en |
dc.identifier.issn |
0162-0134 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/29793 |
en |
dc.description.abstract |
The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP-1339/IT139) has entered clinical trials as the more soluble alternative to the indazolium compound KP1019. In order to get insight into its distribution and accumulation throughout a living organism, KP-1339/IT139 was administered intravenously in non-tumor bearing nude BALB/c mice and the Ru content in blood cells and plasma, bone, brain, colon, kidneys, liver, lung, muscle, spleen, stomach and thymus was determined at several time points. The Ru concentration in blood cells and plasma was found to increase slightly within the first hours of analysis, with the Ru concentration being 3-times higher in plasma compared to blood cells. The plasma samples were subjected to analysis by capillary zone electrophoresis (CZE) and size exclusion/anion exchange chromatography (SEC-IC) both coupled to inductively coupled plasma-mass spectrometry (ICP-MS) and a large majority of the total Ru content was found attached to mouse serum albumin (MSA), confirming similar behavior to KP1019 in an in vivo setting. Within 1h, the peak ratio of approximately 1.2-1.5 Ru per albumin molecule was reached which declined to about 1 Ru per albumin molecule within 24h. Beside the MSA adduct a higher molecular weight species was observed probably stemming from MSA conjugates. In addition, the tissue samples were mineralized by microwave digestion and analyzed for their Ru content. The highest Ru levels were found in colon, lung, liver, kidney and notably in the thymus. The peak Ru concentrations in these tissues were reached 1-6h after administration and declined slowly over time. |
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dc.description.uri |
http://www.journals.elsevier.com/journal-of-inorganic-biochemistry/ |
en |
dc.publisher |
Elsevier |
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dc.relation.ispartofseries |
Journal of Inorganic Biochemistry |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0162-0134/ |
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dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
en |
dc.subject |
Cancer research |
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dc.subject |
Capillary zone electrophoresis |
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dc.subject |
Inductively coupled plasma mass spectrometry |
en |
dc.subject |
Liquid chromatography |
en |
dc.subject |
Ruthenium(III) complexes |
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dc.subject |
Tissue distribution |
en |
dc.title |
Biodistribution of the novel anticancer drug sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] KP-1339/IT139 in nude BALB/c mice and implications on its mode of action |
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dc.type |
Journal Article |
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dc.identifier.doi |
10.1016/j.jinorgbio.2016.02.037 |
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pubs.begin-page |
250 |
en |
pubs.volume |
160 |
en |
dc.description.version |
AM - Accepted Manuscript |
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dc.rights.holder |
Copyright:
Elsevier |
en |
dc.identifier.pmid |
26993078 |
en |
pubs.author-url |
http://www.sciencedirect.com/science/article/pii/S0162013416300630 |
en |
pubs.end-page |
255 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
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pubs.subtype |
Article |
en |
pubs.elements-id |
532648 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Chemistry |
en |
dc.identifier.eissn |
1873-3344 |
en |
dc.identifier.pii |
S0162-0134(16)30063-0 |
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pubs.record-created-at-source-date |
2016-08-04 |
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pubs.dimensions-id |
26993078 |
en |