title: Preclinical evaluation of a radioiodinated fully human antibody for in vivo imaging of vascular adhesion protein-1-positive vasculature in inflammation.
abstract: Vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein mediating leukocyte trafficking from blood to sites of inflammation. BTT-1023 is a fully human monoclonal anti-VAP-1 antibody developed to treat inflammatory diseases. In this study, we preclinically evaluated radioiodinated BTT-1023 for inflammation imaging.
  
  
  METHODS
  Rabbits were intravenously injected with radioiodinated BTT-1023. Distribution and pharmacokinetics were assessed by PET/CT up to 72 h after injection. Human radiation dose estimates for (124)I-BTT-1023 were extrapolated. Additionally, rabbits with chemically induced synovitis were imaged with (123)I-BTT-1023 SPECT/CT.
  
  
  RESULTS
  Radioiodinated BTT-1023 cleared rapidly from blood circulation and distributed to liver and thyroid. Inflamed joints were delineated by SPECT/CT. The estimated human effective dose due to (124)I-BTT-1023 was 0.55 mSv/MBq, if blockage of thyroid uptake is assumed.
  
  
  CONCLUSIONS
  The radioiodinated BTT-1023 was able to detect mild inflammation in vivo. Clinical (124)I-BTT-1023 PET studies with injected radioactivity of 0.5-0.7 MBq/kg may be justified.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Autio
authors.forename: Petri J
authors.initials: PJ
authors.lastname: Vainio
authors.forename: Sami
authors.initials: S
authors.lastname: Suilamo
authors.forename: Antti
authors.initials: A
authors.lastname: Mali
authors.forename: Jani
authors.initials: J
authors.lastname: Vainio
authors.forename: Tiina
authors.initials: T
authors.lastname: Saanijoki
authors.forename: Tommi
authors.initials: T
authors.lastname: Noponen
authors.forename: Helena
authors.initials: H
authors.lastname: Ahtinen
authors.forename: Pauliina
authors.initials: P
authors.lastname: Luoto
authors.forename: Mika
authors.initials: M
authors.lastname: Teräs
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D007457:Iodine Radioisotopes; D057054:Molecular Imaging / Q000379:methods*; D064847:Multimodal Imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D011817:Rabbits; D011829:Radiation Dosage; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007457:Iodine Radioisotopes; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)
keywords: antibody; nuclear imaging; rabbit; radioiodination; vascular adhesion protein-1