NCT03912428 | RECRUITING | Myositis

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 genotypematched 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 participantstients 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).