title: Cellular uptake of radioiodine delivered by trastuzumab can be modified by the addition of epidermal growth factor.
abstract: OBJECTIVE
  The purpose of this study was to analyse whether non-radiolabelled epidermal growth factor (EGF) can modify the cellular uptake of 125I when delivered as [125I]trastuzumab. 125I was used as a marker for the diagnostically and therapeutically more interesting isotopes 123I (SPECT), 124I (PET) and 131I (therapy).
  
  
  METHODS
  The cell-associated radioactivity was measured in squamous carcinoma A431 cells following addition of [125I]trastuzumab. Different concentrations of [125I]trastuzumab and unlabelled EGF were used, and the total, membrane-bound and internalised radioactivity was measured. We also analysed how EGF and trastuzumab affected the cell growth.
  
  
  RESULTS
  It was generally found that the cellular 125I uptake was decreased by the addition of EGF when [125I]trastuzumab was added for short incubation times. However, if the incubation times were longer, EGF increased the 125I uptake. This shift came earlier when higher [125I]trastuzumab concentrations were applied. The addition of EGF also influenced cell proliferation, and concentrations above 10 ng/ml reduced cell growth by approximately 20% after 24 h of incubation.
  
  
  CONCLUSIONS
  By adding unlabelled EGF, it was possible to modify the cellular uptake of [125I]trastuzumab. This points towards new approaches for the modification of radionuclide uptake in EGFR- and HER2-positive tumours.
authors.affiliation: Division of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden. Erika.Nordberg@bms.uu.se
authors.forename: Erika
authors.initials: E
authors.lastname: Nordberg
authors.forename: Ann-Charlott
authors.initials: AC
authors.lastname: Steffen
authors.forename: Mikael
authors.initials: M
authors.lastname: Persson
authors.forename: Asa L
authors.initials: AL
authors.lastname: Sundberg
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008024:Ligands; D049268:Positron-Emission Tomography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D007457:Iodine Radioisotopes; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab