title: 68Ga-DOTA-Siglec-9--a new imaging tool to detect synovitis.
abstract: BACKGROUND
  Vascular adhesion protein-1 (VAP-1) is an adhesion molecule, which upon inflammation is rapidly translocated from intracellular sources to the endothelial cell surface. We have recently discovered that sialic acid- binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1 and that 68Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of 68Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis.
  
  
  METHODS
  Rabbits with synovial inflammation were injected with 18F-FDG or 68Ga-DOTA-Siglec-9 and studied by gamma counting and autoradiography. Certain rabbits were also examined with magnetic resonance imaging (MRI). After PET imaging, rabbits were intravenously administered with anti-VAP-1 antibody to evaluate luminal expression of VAP-1 by immunohistochemistry. Finally, binding of Siglec-9 peptide and VAP-1 positive vessels were evaluated by double staining of rheumatoid arthritis synovium.
  
  
  RESULTS
  Intra-articular injection of hemagglutinin induced mild synovial inflammation in rabbit knee with luminal expression of VAP-1. Synovitis was clearly visualized by 68Ga-DOTA-Siglec-9 PET in addition to 18F-FDG-PET and MRI. Compared with the 18F-FDG, the ex vivo inflamed-to-control synovium ratio of 68Ga-DOTA-Siglec-9 was similar (1.7 ± 0.4 vs. 1.5 ± 0.2, P = 0.32). Double staining revealed that Siglec-9 peptide binds to VAP-1 positive vessels in human rheumatoid synovium.
  
  
  CONCLUSIONS
  Ga-DOTA-Siglec-9 PET tracer detected VAP-1 positive vasculature in the mild synovitis of rabbits comparable with 18F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. hekaah@utu.fi.
authors.forename: Helena
authors.initials: H
authors.lastname: Virtanen
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. akauti@utu.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Autio
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. ralsii@utu.fi.
authors.forename: Riikka
authors.initials: R
authors.lastname: Siitonen
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. halilj@utu.fi.|Turku Center for Disease Modeling, University of Turku, Turku, Finland. halilj@utu.fi.
authors.forename: Heidi
authors.initials: H
authors.lastname: Liljenbäck
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. tiina.saanijoki@utu.fi.
authors.forename: Tiina
authors.initials: T
authors.lastname: Saanijoki
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, University of Turku, Turku, Finland. petteri.lankinen@utu.fi.
authors.forename: Petteri
authors.initials: P
authors.lastname: Lankinen
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. jussma@utu.fi.|Department of Cell Biology and Anatomy, University of Turku, Turku, Finland. jussma@utu.fi.
authors.forename: Jussi
authors.initials: J
authors.lastname: Mäkilä
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. meeri.kakela@utu.fi.
authors.forename: Meeri
authors.initials: M
authors.lastname: Käkelä
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. jarmo.teuho@utu.fi.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Teuho
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. nijosa@utu.fi.
authors.forename: Nina
authors.initials: N
authors.lastname: Savisto
authors.affiliation: VTT Technical Research Centre of Finland, Medical Biotechnology, Turku, Finland. kimmo.jaakkola@fimea.fi.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Jaakkola
authors.affiliation: MediCity Research Laboratory, University of Turku, Turku, Finland. sirpa.jalkanen@utu.fi.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. anne.roivainen@utu.fi.|Turku Center for Disease Modeling, University of Turku, Turku, Finland. anne.roivainen@utu.fi.
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005710:Gallium Radioisotopes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D055550:Protein Stability; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000737:chemistry; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000737:chemistry / Q000378:metabolism; D013585:Synovitis / Q000000981:diagnostic imaging*
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)