Specificity of translocator protein-targeted positron emission tomography in inflammatory joint disease

Objective: Expression 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, [C-11]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study. Methods: Three IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [C-11]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 (SUVr(50-70) bone, SUVr(50-70) blood, respectively) and PET volume of distribution (V-T) of the radioligand were calculated. Results A mean [C-11]PBR28 radioactivity of 378 (range 362-389) MBq was administered. A significant decrease (p < 0.05) in V-T, SUVr(50-70) bone and SUVr(50-70) blood observed after oral emapunil confirmed the TSPO specificity of [C-11]PBR28. A decrease in SUV was not observed in the post-block scan. Conclusion [C-11]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.