title: Studies of KP46 and KP1019 and the Hydrolysis Product of KP1019 in Lipiodol Emulsions: Preparation and Initial Characterizations as Potential Theragnostic Agents.
abstract: BACKGROUND
  Lipiodol (iodized poppy seed oil) accumulates predominately in the tumor rather than in the liver tissue [1, 2]. Therefore, mixing anticancer drugs with Lipiodol may enhance the antitumor effect by increasing the local drug concentration.
  
  
  OBJECTIVE
  In this pilot study, we made use of Lipiodol as a potential carrier of three promising antitumor metal complexes (tris(8-quinolato)gallium(III) (KP46), tetrachlorobis(indazole)ruthenate(III) (KP1019) and the hydrolysis product of KP1019, mer,trans-[RuCl3(H2O)(Hind)2].
  
  
  METHODS
  The stability of the drugs in Lipiodol and the release profile into the aqueous phase were examined independently by three different analytical techniques (high pressure liquid chromatography, HPLC; atom absorption spectroscopy, AAS; and electron spray ionization mass spectrometry, ESI-MS).
  
  
  RESULTS
  The complexes were stable and remained in the Lipiodol emulsion over 3 days. In contrast to KP1019 and KP46, evaluation of Lipiodol emulsions of mer,trans-[RuCl3 (H2O) (Hind) 2] was not possible due to the insolubility of the compound in Lipiodol. KP1019 released rapidly into the aqueous phase in the first week and after 1 month it was not possible to detect the complex in the emulsion. KP46 showed a gradual release with the time resulting in the release of about 6.4 % of KP46 into the aqueous phase after 1 month of incubation.
  
  
  CONCLUSIONS
  The initial results show that Lipiodol can be successfully employed as a carrier of anticancer Ru- or Ga-complexes. Furthermore, advantages can overcome the poor water solubility of the metal complexes, opening new perspectives for the use of Lipiodol emulsions in molecular imaging and cancer therapy as theragnostic agents.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, A-1090 Vienna. Austria.
authors.forename: Irena
authors.initials: I
authors.lastname: Pashkunova-Martic
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, A-1090 Vienna. Austria.
authors.forename: Berta Cebrian
authors.initials: BC
authors.lastname: Losantos
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, A-1090 Vienna. Austria.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kandler
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, A-1090 Vienna. Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions / Q000737:chemistry; D004998:Ethiodized Oil / Q000737:chemistry*; D006868:Hydrolysis; D007191:Indazoles / Q000737:chemistry*; D057054:Molecular Imaging; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000737:chemistry; D010865:Pilot Projects; D017975:Ruthenium Compounds; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D013054:Spectrophotometry, Atomic
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D007191:Indazoles; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III)); C408502:tris(8-quinolinolato)gallium (III); D015125:Oxyquinoline; D004998:Ethiodized Oil
keywords: Antitumor metal complexes; Lipiodol emulsions; drug targeting; gallium; ruthenium; theragnostic agents