Novel PET Radioligand as an Inflammatory Biomarker in Musculoskeletal Conditions
- Conditions
- Rheumatoid ArthritisMyositisInflammatoryHealthy Volunteers
- Interventions
- Drug: 11C-MC1Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) ScanDrug: [11C]ER176
- Registration Number
- NCT03912428
- Lead Sponsor
- National Institute of Mental Health (NIMH)
- Brief Summary
Background:
Inflammation plays a significant role in various disorders that involve neurodegeneration or autoimmune reaction as one of their mechanisms. PET scans can help detect inflammation. Two new drugs may create better PET images.
Objective:
\- To see if the drug \[11C\]MC1 can help image inflammation.
Eligibility:
* People age 18 and older with rheumatoid arthritis or idiopathic inflammatory myopathy (IIM).
* Healthy volunteers enrolled in protocol 01-M-0254 or 17-M-0181 are also needed.
Design:
* Healthy participants will be screened under protocol 01-M-0254 or 17-M-0181.
* Participants with arthritis or IIM will have a screening visit. This will include:
* Medical history
* Physical exam
* Blood and urine tests
* Possible CT or X-ray: A machine will take pictures of the body.
* Healthy participants will have 1 or 2 visits. They may have urine tests. They may take the drug celecoxib by mouth. They will have a PET scan. A small amount of one or both study drugs will be injected through a catheter: A needle will guide a thin plastic tube into an arm vein. Another catheter will draw blood. They will like on a bed that slides into a machine. Their vital signs and heart activity will be measured.
* Participants with arthritis will have up to 2 visits after screening. They may take celecoxib and have PET scans.
* Participants with IIM will have up to 3 visits after screening. At 1 or 2 visits, they will take celecoxib and have PET scans. They will have 1 visit where they have an MRI: They will lie on a table that slides into a machine. The machine takes pictures of the body.
- Detailed Description
I. Objective
18-kDa translocator protein (TSPO) and cyclooxygenase-2 (COX-2) are both implicated in the pathophysiology of various inflammatory disorders, suggesting that both may serve as potential biomarkers of inflammation in brain as well as periphery. Our laboratory recently developed two new radioligands: \[11C\]ER176 to image TSPO and \[11C\]MC1 to image COX-2. Using wholebody imaging, this study seeks to determine whether PET imaging using these new radioligands can differentiate two inflammatory conditions-rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM)-from healthy conditions. To determine if \[11C\]MC1 uptake is specific to COX-2, we will also conduct a blocking study with a selective COX-2 inhibitor (celecoxib) in both \[11C\]MC1 and \[11C\]ER176 scans; celecoxib is expected to block uptake of \[11C\]MC1 but not \[11C\]ER176. Using brain-dedicated imaging, this seeks to determine whether RA patients and healthy volunteers have specific binding in brain - i.e., uptake that can be blocked celecoxib.
II. Study population
Healthy volunteers (n = 17), patients with RA (n = 15), and patients with IIM (n = 15) will undergo whole-body PET/CT scans. Patients with AxSpA (n=15) will undergo two whole-body PET/MRI scans. In addition, healthy volunteers (n = 22) and patients with RA (n = 12) will have brain-dedicated imaging using \[11C\]MC1 concurrent with arterial blood sampling. Finally, 15 patients with RA will be imaged during a period of moderate to severe symptoms and after clinically indicated treatment for two to four months. Thus, the entire population will be healthy volunteers (n = 39), patients with RA (n = 42), patients with AxSpA (n=15) and patients with
IIM (n = 15).
III. Design
1. Phase 1: We will begin by injecting up to 10 mCi of \[11C\]MC1 in one healthy male and one healthy female and then conducting a whole body PET scan. Uptake will be measured in the ovaries and testes, and the dose of radioactivity will be calculated. We will proceed only if the dose to these organs with the higher injected activity proposed for Phase 2 will not exceed the limits specified by the Radioactive Drug Research Committee (RDRC).
2. Phase 2: Fifteen RA patients, 15 IIM patients, and 15 age-, sex-, and genotype-matched healthy subjects will undergo two whole-body PET/CT scans using 15 mCi of \[11C\]ER176 on one day and two whole-body PET/CT scans using 15 mCi of \[11C\]MC1 on another day. The first scan on each day will serve as the baseline scan for comparison; the second scan on each day will be a blocking study using celecoxib. The \[11C\]ER176 scans are not mandatory and will be requested at the discretion of the PI.
3. Phase 3: Twelve RA patients and 22 age- and sex-matched healthy subjects will undergo two brain-dedicated PET/CT scans, each using 20 mCi \[11C\]MC1, and concurrent with arterial blood sampling. The first scan will be a baseline scan, and the second will be after blockade by celecoxib.
4. Phase 4: Fifteen RA patients will be imaged twice with \[11C\]MC: while having moderate to severe symptoms and after clinically-indicated therapy for about two to four months. Participants will have whole-body scan after injection of 15 mCi of \[11C\]MC1.
IV. Outcome measures
For whole body imaging, radioligand uptake in a selected region of interest will be quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight. Possible differences in actual blood radioligand level will be adjusted by venous blood data obtained during the PET scan. Regional uptake after blockade with celecoxib will be expressed as a percentage of the baseline value. The baseline uptake and the percentage blockade by celecoxib of each radioligand will be compared between patients and healthy subjects as well as between inflamed and non-inflamed regions of the body in RA and IIM patients.
For brain-dedicated imaging, the density of COX-2 will be measured with pharmacokinetic modeling and expressed as distribution volume (VT).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 31
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1: Pilot - Whole body scan in health participants 11C-MC1 Healthy participants receive about 10 mCi of \[11C\]MC1 intravenously followed by a whole body PET/CT scan. If radiation dose to selected body organs is within safety limit, Phase 2 of study was initiated Phase 1: Pilot - Whole body scan in health participants Positron Emission Tomography (PET)/computed tomography (CT) Scan Healthy participants receive about 10 mCi of \[11C\]MC1 intravenously followed by a whole body PET/CT scan. If radiation dose to selected body organs is within safety limit, Phase 2 of study was initiated Phase 2: Whole body PET/CT scans in patients 11C-MC1 Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 2: Whole body PET/CT scans in patients Celecoxib Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 2: Whole body PET/CT scans in patients Positron Emission Tomography (PET)/computed tomography (CT) Scan Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 2: Whole body PET/CT scans in healthy participants 11C-MC1 Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]ER176 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 2: Whole body PET/CT scans in healthy participants Celecoxib Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]ER176 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 2: Whole body PET/CT scans in healthy participants [11C]ER176 Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]ER176 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 2: Whole body PET/CT scans in healthy participants Positron Emission Tomography (PET)/computed tomography (CT) Scan Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]ER176 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. Phase 3: Brain PET/CT scans in healthy participants 11C-MC1 Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi \[11C\]MC1 followed by a second brain PET/CT scan with 20 mCi \[11C\]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan. Phase 3: Brain PET/CT scans in healthy participants Celecoxib Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi \[11C\]MC1 followed by a second brain PET/CT scan with 20 mCi \[11C\]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan. Phase 3: Brain PET/CT scans in healthy participants Positron Emission Tomography (PET)/computed tomography (CT) Scan Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi \[11C\]MC1 followed by a second brain PET/CT scan with 20 mCi \[11C\]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan.
- Primary Outcome Measures
Name Time Method Uptake of [11C]MC1 by Organs Up to 120 minutes during each scan Participant received whole body PET/CT scan and radioligand uptake of \[11C\]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.
Uptake of [11C]MC1 by Organs - Gender Specific Organs Up to 120 minutes during each scan Participant received whole body PET/CT scan and radioligand uptake of \[11C\]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.
Phase 2: [11C]MC1 Binding in Inflamed Body Parts - HANDS Up to 120 minutes during each scan The uptake of \[11C\]MC1 before (baseline) and after blockade by single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Phase 2: [11C]MC1 Binding in Non-inflamed Body Parts - HANDS Up to 120 minutes during each scan The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Phase 2: [11C]MC1 Binding in Inflamed Body Parts - KNEES Up to 120 minutes during each scan The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Phase 2: [11C]MC1 Binding Between Non-inflamed Body - KNEES Up to 120 minutes during each scan The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.
Whole Brain Volume of Distribution (VT)/ Free-fraction (fP) of [11C]MC1 Up to 120 minutes during each scan The volume of distribution (VT) of \[11C\]MC1 measured as the brain-to-plasma ratio using the 2-tissue compartmental modeling divided by free-fraction in the plasma of parent radioligand (fP) at baseline and two hours after blockade with single dose of 600 mg celecoxib orally.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center🇺🇸Bethesda, Maryland, United States