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

Study Overview
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Brief Summary
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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
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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.

Official Title
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PET/CT Study of Biodistribution and Performance of the [68Ga]Ga-DOTA-Siglec-9 in Patients With Rheumatoid Arthritis,Vasculitis or Pulmonary Sarcoidosis, and Radiation Dosimetry, Pharmacokinetics, Biodistribution, Safety and Tolerability in Healthy Men

Conditions
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Vasculitis, Healthy Subjects, Rheumatoid Arthritis, Pulmonary Sarcoidosis

Intervention / Treatment
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* Other: [68Ga]Ga-DOTA-Siglec-9


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Whole-body distribution, plasma pharmacokinetics, radiation dosimetry, safety, tolerability and performance of [68Ga]Ga-DOTA-Siglec-9
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: [68Ga]Ga-DOTA-Siglec-9<br>Intravenous 140 MBq bolus injection of [68Ga]Ga-DOTA-Siglec-9 radiopharmaceutical | Other: [68Ga]Ga-DOTA-Siglec-9<br>* Vascular Adhesion Protein 1 (VAP-1) targeted radiopharmaceutical<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole-body distribution of [68Ga]Ga-DOTA-Siglec-9 | Knowledge how intravenously injected [68Ga]Ga-DOTA-Siglec-9 is distributed in human body | within a day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation dosimetry of [68Ga]Ga-DOTA-Siglec-9 | Absorbed ionisation radiation dose in critical organs due to single intravenous 140 megabecquerel injection of [68Ga]Ga-DOTA-Siglec-9 | within a week |