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

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 (68)Ga-labeled Siglec-9 motif peptide facilitates in vivo imaging of inflammation. This study evaluated the feasibility of (68)Ga-DOTA-Siglec-9 positron emission tomography (PET) for the assessment of synovitis. METHODS: Rabbits with synovial inflammation were injected with (18)F-FDG or (68)Ga-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 (68)Ga-DOTA-Siglec-9 PET in addition to (18)F-FDG-PET and MRI. Compared with the (18)F-FDG, the ex vivo inflamed-to-control synovium ratio of (68)Ga-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 (18)F-FDG, suggesting its potential for in vivo imaging of synovial inflammation in patients with rheumatic diseases.