Biodistribution, Dosimetry and Performance of [68Ga]Ga-DOTA-Siglec-9 in Healthy and Patients With Rheumatoid Arthritis, Vasculitis or Pulmonary Sarcoidosis

Vascular adhesion protein 1 (VAP-1) is an inflammation inducible endothelial cell molecule mediating leukocyte trafficking from blood into the sites of inflammation. Although VAP-1 plays important role in early phases of inflammation, its luminal expression on the endothelium will remain constant if the inflammation continues, which suggest VAP-1 as a promising target for molecular imaging of inflammation. We have previously shown that sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a VAP-1 ligand, and the gallium-68 labeled 1,4,7,10-tetraazacyclododecane-N,N´,N´´,N´´´-tetraacetic acid conjugated peptide ([68Ga]Ga-DOTA-Siglec-9) containing residues 283-297 from Siglec-9 can be used for PET imaging of inflammation in various experimental models. This first-in-human study evaluates safety, tolerability, biodistribution and performance of [68Ga]Ga-DOTA-Siglec-9 after single intravenous injection in six healthy volunteers, and in ten patients with active rheumatoid arthritis (RA), five patients with vasculitis and five patients with pulmonary sarcoidosis.

Inclusion criteria

• Healthy 18-70 year-old men
• Male or female 18-70 year-old patients with active rheumatoid arthritis, vasculitis or pulmonary sarcoidosis

Exclusion criteria

• In healthy: ongoing infection/inflammation proven by blood or other tests
• In patients with rheumatoid arthritis: no treatment with disease-modifying anti-rheumatic drugs or biologic agents, and no corticosteroids for 2 weeks prior the study
• In patients with vasculitis: no immunosuppressives, and glucocorticoid less than 60 mg for 2 weeks or NSAIDs for 1 day prior the study
• In patients with pulmonary sarcoidosis: no corticosteroids for 1 week or NSAIDs for day prior the study