title: Imaging of platelet-derived growth factor receptor β expression in glioblastoma xenografts using affibody molecule 111In-DOTA-Z09591.
abstract: The overexpression and excessive signaling of platelet-derived growth factor receptor β (PDGFRβ) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFRβ expression might help to select PDGFRβ targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFRβ expression using an Affibody molecule, a small nonimmunoglobulin affinity protein.
  
  
  METHODS
  The PDGFRβ-binding Z09591 Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. Targeting of the PDGFRβ-expressing U-87 MG glioblastoma cell line using (111)In-DOTA-Z09591 was evaluated in vitro and in vivo.
  
  
  RESULTS
  DOTA-Z09591 was stably labeled with (111)In with preserved specific binding to PDGFRβ-expressing cells in vitro. The dissociation constant for (111)In-DOTA-Z09591 binding to U-87 MG cells was determined to be 92 ± 10 pM. In mice bearing U-87 MG xenografts, the tumor uptake of (111)In-DOTA-Z09591 was 7.2 ± 2.4 percentage injected dose per gram and the tumor-to-blood ratio was 28 ± 14 at 2 h after injection. In vivo receptor saturation experiments demonstrated that targeting of U-87 MG xenografts in mice was PDGFRβ-specific. U-87 MG xenografts were clearly visualized using small-animal SPECT/CT at 3 h after injection.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of in vivo visualization of PDGFRβ-expressing xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical imaging tool for PDGFRβ expression during various pathologic conditions.
authors.affiliation: Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Varasteh
authors.forename: Hadis
authors.initials: H
authors.lastname: Honarvar
authors.forename: Seyed Jalal
authors.initials: SJ
authors.lastname: Hosseinimehr
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
authors.forename: Per
authors.initials: P
authors.lastname: Jonasson
authors.forename: Fredrik Y
authors.initials: FY
authors.lastname: Frejd
authors.forename: Lars
authors.initials: L
authors.lastname: Abrahmsen
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D064847:Multimodal Imaging / Q000379:methods; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: C587625:111In-DOTA-Z09591; D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D011993:Recombinant Fusion Proteins; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: 111In; Affibody molecule; PDGFRβ; U-87 MG xenograft; molecular imaging