title: X-ray absorption spectroscopy of an investigational anticancer gallium(III) drug: interaction with serum proteins, elemental distribution pattern, and coordination of the compound in tissue.
abstract: Tris(8-quinolinolato)gallium(III) (1, KP46) is a very promising investigational anticancer drug. Its interaction with serum proteins, elemental distribution, and coordination in tissue were investigated with X-ray absorption (XAS) methods. Model compounds with mixed O, N, and/or S donor atoms are reported. The coordination and structure of 1 in cell culture medium (minimum essential medium, MEM) and fetal calf serum (FCS) were probed by XANES and EXAFS. The interaction of 1 with the serum proteins apotransferrin (apoTf) and human serum albumin (HSA) was addressed as well. By application of micro-XAS to tissue samples from mice treated with 1, the gallium distribution pattern was analyzed and compared to those of physiological trace elements. The complex 1 turned out to be very stable under physiological conditions, in cell culture media and in tissue samples. The coordination environment of the metal center remains intact in the presence of apoTf and HSA. The gallium distribution pattern in tumor and liver tissue revealed high similarities to the distribution patterns of Zn and Fe, minor similarities to Cu and Ni, and no similarity to Ca.
authors.affiliation: Institut für Biophysikalische Chemie, Universität Wien, Althanstraße 14, 1090 Wien, Austria.
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Hummer
authors.forename: Caroline
authors.initials: C
authors.lastname: Bartel
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.forename: Wolfram
authors.initials: W
authors.lastname: Meyer-Klaucke
authors.forename: Tina
authors.initials: T
authors.lastname: Geraki
authors.forename: Paul D
authors.initials: PD
authors.lastname: Quinn
authors.forename: Ana
authors.initials: A
authors.lastname: Mijovilovich
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Annette
authors.initials: A
authors.lastname: Rompel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001059:Apoproteins / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000493:pharmacokinetics; D015507:Drugs, Investigational / Q000737:chemistry / Q000493:pharmacokinetics; D005708:Gallium; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives; D012510:Sarcoma 180 / Q000378:metabolism; D044967:Serum; D012709:Serum Albumin / Q000737:chemistry; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry; D056928:X-Ray Absorption Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D001059:Apoproteins; D001798:Blood Proteins; D056831:Coordination Complexes; D015507:Drugs, Investigational; D009942:Organometallic Compounds; D012709:Serum Albumin; D014168:Transferrin; C028284:apotransferrin; C408502:tris(8-quinolinolato)gallium (III); D015125:Oxyquinoline; D005708:Gallium