title: Targeting against epidermal growth factor receptors. Cellular processing of astatinated EGF after binding to cultured carcinoma cells.
abstract: BACKGROUND
  The alpha-emitting nuclide 211At is of great interest for radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g. epidermal growth factor (EGF) the receptors of which are overexpressed in many malignancies. However, almost no information concerning the cellular processing of astatinated targeting agents is available.
  
  
  METHODS
  We indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular processing in A-431 carcinoma cells in comparison with data concerning [125I]-benzoate-EGF.
  
  
  RESULTS
  The biological half-life of astatine (3.5 h) was longer than the half-life of the iodine label (1.5 h). The increase of the half-life was due to longer retention of the internalised astatine radioactivity. The maximum accumulation for the astatine label occurred later (4-6h) than that for the iodine label (2-4h), indicating a slower excretion of astatine that was confirmed in experiment with 211At/1251-benzoate-EGF.
  
  
  CONCLUSIONS
  The long retention of astatine might be advantageous for radionuclide therapy.
authors.affiliation: Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Anna.Orlova@bms.uu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
authors.forename: Anna
authors.initials: A
authors.lastname: Sjöstrom
authors.forename: Ondrej
authors.initials: O
authors.lastname: Lebeda
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Jorgen
authors.initials: J
authors.lastname: Carlsson
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
mesh_terms: D001246:Astatine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D002277:Carcinoma / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000493:pharmacokinetics*; D015622:Epithelioid Cells / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007463:Iodobenzoates / Q000378:metabolism / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D007463:Iodobenzoates; D019275:Radiopharmaceuticals; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D001246:Astatine