title: Synthesis and Evaluation of a Zr-89-Labeled Monoclonal Antibody for Immuno-PET Imaging of Amyloid-β Deposition in the Brain.
abstract: The aim of this study was to evaluate the in vitro and in vivo characteristics of [(89)Zr]JRF/AβN/25, a radiolabeled monoclonal antibody directed against amyloid-β (Aβ).
  
  
  
  JRF/AβN/25 was labeled with (89)Zr following modification with desferal. The affinity of the tracer for Aβ1-40 was determined in a saturation binding assay. In vitro stability was evaluated, and in vivo plasma stability and biodistribution of [(89)Zr]Df-Bz-JRF/AβN/25 were determined in wild-type mice. To evaluate whether the antibody can cross the blood-brain barrier, brain uptake in wild-type mice was additionally assessed by ex vivo autoradiography.
  
  
  
  [(89)Zr]Df-Bz-JRF/AβN/25 was obtained in an average radiochemical yield of 50 % and a radiochemical purity of >97 %. A saturation binding assay demonstrated specific binding of [(89)Zr]Df-Bz-JRF/AβN/25 to Aβ1-40 with nanomolar affinity. The tracer was stable in buffer and proved to be stable in vivo with >92 % intact monoclonal antibody (mAb) remaining in the plasma at 48 h post injection. A biodistribution study showed a slow blood clearance with no significant accumulation of activity in any of the organs. Furthermore, [(89)Zr]Df-Bz-JRF/AβN/25 demonstrated modest brain penetration, which slowly decreased in time. This cerebral uptake was confirmed by ex vivo autoradiography.
  
  
  
  [(89)Zr]Df-Bz-JRF/AβN/25 binds with high affinity to Aβ1-40. The tracer displays an acceptable in vivo stability and is able to cross the blood-brain barrier. [(89)Zr]Df-Bz-JRF/AβN/25 might therefore be a potential candidate for in vivo imaging of Aβ deposition in the brain.
authors: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
authors: Jens
authors: J
authors: Fissers
authors: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Department of Translational Neurosciences, University of Antwerp, Antwerp, Belgium.
authors: Ann-Marie
authors: AM
authors: Waldron
authors: Pharmaceutical Development & Manufacturing Sciences, Janssen Pharmaceutica NV, Beerse, Belgium.
authors: Thomas
authors: T
authors: De Vijlder
authors: Neuroscience Discovery Department, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Antwerp, Belgium.
authors: Bianca
authors: B
authors: Van Broeck
authors: Department of Experimental Medicine, Janssen Pharmaceutica NV, Beerse, Belgium.
authors: Darrel J
authors: DJ
authors: Pemberton
authors: Neuroscience Discovery Department, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Antwerp, Belgium.
authors: Marc
authors: M
authors: Mercken
authors: Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
authors: Pieter
authors: P
authors: Van Der Veken
authors: Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
authors: Jurgen
authors: J
authors: Joossens
authors: Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
authors: Koen
authors: K
authors: Augustyns
authors: Department of Translational Neurosciences, University of Antwerp, Antwerp, Belgium.
authors: Stefanie
authors: S
authors: Dedeurwaerdere
authors: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors: Sigrid
authors: S
authors: Stroobants
authors: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors: Steven
authors: S
authors: Staelens
authors: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium. leonie.wyffels@uza.be.|Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium. leonie.wyffels@uza.be.
authors: Leonie
authors: L
authors: Wyffels
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging*; D003676:Deferoxamine / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods*; D013194:Staining and Labeling; D014018:Tissue Distribution; D015040:Zirconium / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D015040:Zirconium; D003676:Deferoxamine
keywords: Amyloid-β; PET; [89Zr]-Df-Bz-JRF/AβN/25