Abstract
ObjectiveExpression of the translocator protein (TSPO) on inflammatory cells has facilitated imaging of synovitis with TSPO-targeted positron emission tomography (PET). We aimed to quantitatively assess the specificity of the second-generation TSPO PET radioligand, [11C]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study.MethodsThree IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [11C]PBR28-PET scans before and after administration of 90 mg of oral emapunil (XBD-173), a TSPO ligand the same day. Radial arterial blood sampling was performed throughout the scan, and total radioactivity and radioactive metabolites were obtained. A semi-automated method was used to generate regions of interest. Standardized uptake value (SUV) and SUV ratio corrected for activity in bone and blood between 50 and 70 min (SUVr50–70 bone, SUVr50–70 blood, respectively) and PET volume of distribution (VT) of the radioligand were calculated.ResultsA mean [11C]PBR28 radioactivity of 378 (range 362–389) MBq was administered. A significant decrease (p < 0.05) in VT, SUVr50–70 bone and SUVr50–70 blood observed after oral emapunil confirmed the TSPO specificity of [11C]PBR28. A decrease in SUV was not observed in the post-block scan.Conclusion[11C]PBR28 is TSPO-specific radioligand in IJD patients. Simplified PET protocols with static PET acquisition can be used in the management and evaluation of novel therapeutics that target TSPO overexpressing cells.
Highlights
Synovial envelope of the articular joint is a critical provider of synovial fluid components and articular cartilage nutrients
Review of the time–activity curves (TAC) (Fig. 2) demonstrated a plateauing in [11C]PBR28 Standardized uptake value (SUV) between 50- and 70-min post-radioligand injection; SUV and Standardized uptake value ratio (SUVr) were calculated between these time points for all subjects
positron emission tomography (PET) parameters that account for peripheral distribution of the radioligand such as volume of distribution (VT), SUVr50–70 blood and SUVr50–70 bone showed a significant decrease in radioligand uptake in the synovium with mean (SD) respective pre- and post-block ligand uptake for VT being (4.84 (0.54) versus 2.69 (0.80); p < 0.05), for SUVr50–70 blood (3.67 (1.29) versus 2.22 (0.32); p < 0.05) and for SUVr50–70 bone (3.12 (1.03) versus 2.10 (0.20); p < 0.05)
Summary
Synovial envelope of the articular joint is a critical provider of synovial fluid components and articular cartilage nutrients. Synovial inflammation (synovitis) together with progressive degeneration of articular cartilage is key pathological features in a variety of inflammatory joint diseases (IJDs), as diverse as rheumatoid (RA), psoriatic, juvenile and idiopathic arthritis, lupus and gout and a significant contributor of articular cartilage degeneration in osteoarthritis (OA) [1]. Synovial inflammatory infiltrate is composed of aggressive macrophage- and fibroblast-like. Detection and treatment of subclinical or early inflammatory arthritis is likely to prevent disease progression, permanent joint damage and associated comorbidity. Subclinical or early disease is often difficult to detect, leading to a delay in diagnosis [4]. The assessment of response to treatment of inflammatory disease is often based on composite disease activity scores, which can be highly subjective and difficult to reproduce consistently. An unmet clinical need is to functionally evaluate the target tissue and assess changes in the infiltrate for quantitative assessment and to evaluate targeted therapies
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