title: Imaging of insulinlike growth factor type 1 receptor in prostate cancer xenografts using the affibody molecule 111In-DOTA-ZIGF1R:4551.
abstract: One of the pathways leading to androgen independence in prostate cancer involves upregulation of insulinlike growth factor type 1 receptor (IGF-1R). Radionuclide imaging of IGF-1R in tumors might be used for selection of patients who would most likely benefit from IGF-1R-targeted therapy. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of IGF-1R expression in prostate cancer xenografts using a small nonimmunoglobulin-derived binding protein called an Affibody molecule.
  
  
  METHODS
  The IGF-1R-binding Z(IGF1R:4551) Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. The binding of radiolabeled Z(IGF1R:4551) to IGF-1R-expressing cells was evaluated in vitro and in vivo.
  
  
  RESULTS
  DOTA-Z(IGF1R:4551) can be stably labeled with (111)In with preserved specific binding to IGF-1R-expressing cells in vitro. In mice, (111)In-DOTA-Z(IGF1R:4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung, and salivary gland). Receptor saturation experiments demonstrated that targeting of DU-145 prostate cancer xenografts in NMRI nu/nu mice was IGF-1R-specific. The tumor uptake was 1.1 ± 0.3 percentage injected dose per gram, and the tumor-to-blood ratio was 3.2 ± 0.2 at 8 h after injection.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of in vivo targeting of IGF-1R-expressing prostate cancer xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical tool for stratification of patients with prostate cancer for IGF-1R-targeting therapy.
authors.affiliation: Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Vladimir.Tolmachev@bms.uu.se
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Jennie
authors.initials: J
authors.lastname: Malmberg
authors.forename: Camilla
authors.initials: C
authors.lastname: Hofström
authors.forename: Lars
authors.initials: L
authors.lastname: Abrahmsén
authors.forename: Thomas
authors.initials: T
authors.lastname: Bergman
authors.forename: Anna
authors.initials: A
authors.lastname: Sjöberg
authors.forename: Mattias
authors.initials: M
authors.lastname: Sandström
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Gräslund
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005240:Feasibility Studies; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D011877:Radionuclide Imaging; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D011993:Recombinant Fusion Proteins; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D017526:Receptor, IGF Type 1