Ankylosing Spondylitis PET Imaging and Quantifications via P2X7 Receptor-Targeting Radioligand [18F]GSK14260

Abstract

Abstract Purpose Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial spine that manifests with various clinical signs and symptoms; however, the quantitative detection of inflammation in AS remains a drawback in clinical settings. We aimed to investigate the feasibility of using a specific P2X7R-targeting 18F-labeled tracer [18F]GSK1482160 for positron emission tomography (PET) imaging and the quantification of AS. Methods The radioligand [18F]GSK1482160 was obtained based on nucleophilic aromatic radiofluorination with [18F]fluoride. Dynamic [18F]GSK1482160 and [18F]FDG micro-PET/CT imaging were performed on AS mouse models and age-matched controls. Tracer kinetics modeling was performed using Logan graphical arterial input function analysis and Patlak models to quantify the in vivo expression of P2X7R and the influx rate of [18F]FDG, respectively. The post-PET tissues were collected for hematoxylin-eosin, immunohistochemical (IHC), and immunofluorescence (IF) staining. Results The decay-corrected radiochemical yield (RCY) of [18F]GSK1482160 was 20–30%; radiochemical purity, ≥ 98%; and molar activity, 55–85 GBq/µmol. [18F]GSK1482160 PET/CT imaging revealed that the specific binding in the ankle joint and sacroiliac joint (SIJ) of the AS group (BPNDankle = 13.75 ± 2.20, BPND SIJ = 15.87 ± 3.90) were significantly higher than that of the control group (BPNDankle = 0.14 ± 0.08, BPNDSIJ = 0.75 ± 0.48). In contrast, in [18F]FDG imaging, there was no significant difference in the uptake in the ankle joint and SIJ between the two groups. 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 pathogenesis of inflammation in human AS. Conclusion This study developed a novel P2X7R-targeting PET tracer [18F]GSK1482160 to detect the expression of P2X7R in AS mouse models and provided a powerful non-invasive PET imaging and quantification for AS.