Ankylosing spondylitis PET imaging and quantifications via P2X7 receptor-targeting radioligand [ 18 F]GSK1482160

Purpose Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine; however, the quantitative detection of inflammation in AS remains a challenge in clinical settings. We aimed to investigate the feasibility of using a specific P2X7R-targeting 18 F-labeled tracer [ 18 F]GSK1482160 for positron emission tomography (PET) imaging and the quantification of AS. Methods The radioligand [ 18 F]GSK1482160 was obtained based on nucleophilic aliphatic substitution. Dynamic [ 18 F]GSK1482160 and [ 18 F]FDG micro-PET/CT imaging were performed on AS mice ( n = 8) and age-matched controls ( n = 8). Tracer kinetics modeling was performed using Logan’s graphical arterial input function analysis to quantify the in vivo expression of P2X7R. The post-PET tissues were collected for hematoxylin–eosin (H&E), immunohistochemical (IHC), and immunofluorescence (IF) staining. Results [ 18 F]GSK1482160 PET/CT imaging revealed that the specific binding in the ankle joint and sacroiliac joint (SIJ) of the AS at 8 weeks group (BP ND ankle−AS−8W (non-displaceable binding potential of the ankle) 3.931 ± 0.74; BP ND SIJ−AS−8W (BP BD of the SIJ) 4.225 ± 0.84) were significantly higher than the controls at 8 weeks group (BP ND ankle−Ctr−8W 0.325 ± 0.15, BP ND SJJ−Ctr−8W 0.319 ± 0.17) respectively, and the AS at 14 weeks group (BP ND ankle−AS−14W 12.212 ± 2.25; BP ND SJJ−AS−14W 13.389 ± 3.60) were significantly higher than the controls at 14 weeks group (BP ND ankle−Ctr−14W 0.204 ± 0.16, BP ND SJJ−Ctr−14W 0.655 ± 0.35) respectively. The four groups had no significant difference in the [ 18 F]FDG uptake of ankle and SIJ. IHC and IF staining revealed that the overexpression of P2X7R was colocalized with activated macrophages from the ankle synovium and spinal endplate in mice with AS, indicating that quantification of P2X7R may contribute to the understanding of the pathogenesis of inflammation in human AS. Conclusion This study developed a novel P2X7R-targeting PET tracer [ 18 F]GSK1482160 to detect the expression of P2X7R in AS mouse models and provided powerful non-invasive PET imaging and quantification for AS.