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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis; Vasculitis; Healthy Subjects; Pulmonary Sarcoidosis
• Intervention / Treatment: Other: [68Ga]Ga-DOTA-Siglec-9

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 Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • Turku University Hospital, Turku PET Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Anne Roivainen, Professor, Turku University Hospital, Turku PET Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2018
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 23, 2018
• First Submitted That Met QC Criteria: November 23, 2018
• First Posted (Actual): November 27, 2018

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Lung Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Lung Diseases, Interstitial; Arthritis; Arthritis, Rheumatoid; Vasculitis; Sarcoidosis, Pulmonary; Sarcoidosis
• Other Study ID Numbers: T282/2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No