PMID- 26993078
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20220321
IS  - 1873-3344 (Electronic)
IS  - 0162-0134 (Linking)
VI  - 160
DP  - 2016 Jul
TI  - 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.
PG  - 250-5
LID - S0162-0134(16)30063-0 [pii]
LID - 10.1016/j.jinorgbio.2016.02.037 [doi]
AB  - 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.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Bytzek, Anna K
AU  - Bytzek AK
AD  - University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, 
      Waehringer Str. 42, A-1090, Vienna, Austria.
FAU - Koellensperger, Gunda
AU  - Koellensperger G
AD  - University of Vienna, Faculty of Chemistry, Institute of Analytical Chemistry, 
      Waehringer Str. 38, A-1090, Vienna, Austria.
FAU - Keppler, Bernhard K
AU  - Keppler BK
AD  - University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, 
      Waehringer Str. 42, A-1090, Vienna, Austria; University of Vienna, Research 
      Platform 'Translational Cancer Therapy Research', Waehringer Str. 42, A-1090, 
      Vienna, Austria.
FAU - G Hartinger, Christian
AU  - G Hartinger C
AD  - University of Vienna, Faculty of Chemistry, Institute of Inorganic Chemistry, 
      Waehringer Str. 42, A-1090, Vienna, Austria; University of Vienna, Research 
      Platform 'Translational Cancer Therapy Research', Waehringer Str. 42, A-1090, 
      Vienna, Austria; University of Auckland, School of Chemical Sciences, Private Bag 
      92019, Auckland 1142, New Zealand. Electronic address: 
      c.hartinger@auckland.ac.nz.
LA  - eng
PT  - Journal Article
DEP - 20160303
PL  - United States
TA  - J Inorg Biochem
JT  - Journal of inorganic biochemistry
JID - 7905788
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Indazoles)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Ruthenium Compounds)
RN  - 0 (Serum Albumin)
RN  - 0 (indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III)))
RN  - 7UI0TKC3U5 (Ruthenium)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/blood/*pharmacokinetics
MH  - Colon/metabolism
MH  - Indazoles/blood/*pharmacokinetics
MH  - Kidney/metabolism
MH  - Liver/metabolism
MH  - Lung/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Organ Specificity
MH  - Organometallic Compounds/blood/*pharmacokinetics
MH  - Protein Binding
MH  - Ruthenium/*blood
MH  - Ruthenium Compounds
MH  - Serum Albumin/metabolism
MH  - Thymus Gland/metabolism
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Cancer research
OT  - Capillary zone electrophoresis
OT  - Inductively coupled plasma mass spectrometry
OT  - Liquid chromatography
OT  - Ruthenium(III) complexes
OT  - Tissue distribution
EDAT- 2016/03/20 06:00
MHDA- 2017/06/27 06:00
CRDT- 2016/03/20 06:00
PHST- 2015/10/13 00:00 [received]
PHST- 2016/02/23 00:00 [revised]
PHST- 2016/02/28 00:00 [accepted]
PHST- 2016/03/20 06:00 [entrez]
PHST- 2016/03/20 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
AID - S0162-0134(16)30063-0 [pii]
AID - 10.1016/j.jinorgbio.2016.02.037 [doi]
PST - ppublish
SO  - J Inorg Biochem. 2016 Jul;160:250-5. doi: 10.1016/j.jinorgbio.2016.02.037. Epub 
      2016 Mar 3.