title: Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy.
abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma). With the exception of one lipid (B-THF-14), the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids precludes their use in boron neutron capture therapy.
authors.affiliation: Department of Chemistry, University of Bremen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schaffran
authors.affiliation: Department of Chemistry, University of Bremen, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Institute of Neuropathology, Klinikum Bremen-Mitte, Germany ; Cooperative Center Medicine, University of Bremen, Bremen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bergmann
authors.affiliation: "In-vivo-MR" AG, FB2, University of Bremen, Bremen, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Küstermann
authors.affiliation: Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Süss
authors.affiliation: Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Unversitaet Muenchen, Garching, Germany.
authors.forename: Franz M
authors.initials: FM
authors.lastname: Wagner
authors.affiliation: Department of Biochemistry, Alexandria University, Alexandria, Egypt.
authors.forename: Doaa
authors.initials: D
authors.lastname: Awad
authors.affiliation: Department of Chemistry, University of Bremen, Germany ; Institute of Neuropathology, Klinikum Bremen-Mitte, Germany ; School of Engineering and Science, Jacobs University Bremen, Bremen, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Gabel
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects* / Q000379:methods; D006470:Hemorrhage / Q000139:chemically induced* / Q000473:pathology; D006651:Histocytochemistry; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology* / Q000532:radiotherapy*; D014018:Tissue Distribution
chemical_list: D001896:Boron Compounds; D008055:Lipids; D008081:Liposomes; C119788:dodecaborate
keywords: histology; liposomes; magnetic resonance imaging; pharmacodynamics
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