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

Not Applicable

• Conditions: Rheumatoid Arthritis; Pulmonary Sarcoidosis; Healthy Subjects; Vasculitis
• Interventions: Other: [68Ga]Ga-DOTA-Siglec-9

• Registration Number: NCT03755245
• Lead Sponsor: Turku University Hospital

Brief Summary

This study evaluates safety, tolerability, biodistribution and performance of the \[68Ga\]Ga-DOTA-Siglec-9 following a single intravenous administration in patients with active rheumatoid arthritis, vasculitis or pulmonary sarcoidosis as well as radiation dosimetry, plasma pharmacokinetics, biodistribution, safety and tolerability of the tracer in healthy volunteers.

Detailed Description

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.

Study Timeline

• Study Start: 2018-11-23
• Study First Submitted: 2018-11-23
• Study First Submitted QC: 2018-11-23
• Study First Posted: 2018-11-27
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-25
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[68Ga]Ga-DOTA-Siglec-9	[68Ga]Ga-DOTA-Siglec-9	Intravenous 140 MBq bolus injection of \[68Ga\]Ga-DOTA-Siglec-9 radiopharmaceutical

Primary Outcome Measures

Name	Time	Method
Whole-body distribution of [68Ga]Ga-DOTA-Siglec-9	within a day	Knowledge how intravenously injected \[68Ga\]Ga-DOTA-Siglec-9 is distributed in human body

Secondary Outcome Measures

Name	Time	Method
Radiation dosimetry of [68Ga]Ga-DOTA-Siglec-9	within a week	Absorbed ionisation radiation dose in critical organs due to single intravenous 140 megabecquerel injection of \[68Ga\]Ga-DOTA-Siglec-9

Trial Locations

Locations (1)

Turku University Hospital, Turku PET Centre; 🇫🇮 Turku, Finland