68Ga-DOTA-Siglec-9--a new imaging tool to detect synovitis

Arthritis Res Ther. 2015 Nov 3:17:308. doi: 10.1186/s13075-015-0826-8.


Introduction: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amine Oxidase (Copper-Containing) / chemistry
  • Amine Oxidase (Copper-Containing) / metabolism
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / metabolism
  • Arthritis, Rheumatoid / diagnostic imaging
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Gallium Radioisotopes* / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Immunohistochemistry
  • Male
  • Positron-Emission Tomography / methods*
  • Protein Stability
  • Rabbits
  • Radiopharmaceuticals* / chemistry
  • Sialic Acid Binding Immunoglobulin-like Lectins / chemistry
  • Sialic Acid Binding Immunoglobulin-like Lectins / metabolism
  • Synovitis / diagnostic imaging*


  • Antigens, CD
  • Cell Adhesion Molecules
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Radiopharmaceuticals
  • SIGLEC9 protein, human
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • AOC3 protein, human
  • Amine Oxidase (Copper-Containing)