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

Abstract

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, [11C]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 [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. Results A 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.

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

“…In one study, head-to-head comparisons of 3 radiotracers provided a clear demonstration of increased target-to-background ration with [ 11 C]DPA-713 [ 27 ]. Successful blocking of [ 11 C]PBR28 binding with XBD173 was reported very recently [ 201 ]. Finally, the involvement of the brain immune system in RA was recently explored with [ 11 C]PBR28 [ 202 ], but no differences in TSPO binding were detected in RA vs controls.…”

“…Hence, cornerstone studies on TSPO PET imaging would definitely benefit from replication. Finally, of particular importance are rare but highly-informative reports such as i) blocking studies with newly approved TSPO ligands like XBD173 [ 105 , 201 , 242 ], ii) double-tracer studies (12 records).…”

“…TSPO PET allowed the detection of active clinical but also subclinical synovitis in joints (knees, wrists, hands). After 3 initials (R)-[ 11 C]PK11195 studies which used a short static scan and scoring scale to assess overall uptake on multiple joints [196][197][198], there was a renewed interest in this pathology driven by the use of various challengers and SUV quantification [27,[199][200][201]. In one study, head-to-head comparisons of 3 radiotracers provided a clear demonstration of increased target-to-background ration with [ 11 C] DPA-713 [27].…”

Molecular imaging for evaluation of synovitis associated with osteoarthritis: a narrative review

“…A PET scan using TSPO targeting radiotracer, [ 11 C] PBR28 was assessed for its specificity to TSPO in a patient with OA, where it was found to bind specifically to lesions rich in TSPO in a patient with OA [ 40 ]. Folate receptor (FR) targeting radiotracers have also detected macrophage activation in experimental OA using diethylenetriaminepentaacetic acid (DTPA)–folate [ 52 ].…”

Development and validation of cuproptosis-related genes in synovitis during osteoarthritis progress

“…Recently, the goals of OA prevention and treatment have expanded to focus on the cartilage microenvironment. The synovium is one of the key constituents of the cartilage microenvironment ( 3 , 4 ). Synovium serves as a two-way bridge for nutrients and the clearance of waste between the cartilage and bloodstream ( 5 ).…”