Increased Fibroblast-Like Synoviocyte Inflammation in Rheumatoid Arthritis Revealed by Sphingosine 1-Phosphate Receptor 1-Targeting PET/CT Imaging

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation. This study aimed to use the sphingosine 1-phosphate receptor 1 (S1PR1) targeted tracer [¹⁸F]TZ4877 with PET/CT to assess synovial inflammation in a collagen-induced arthritis (CIA) mouse model. [¹⁸F]TZ4877 and [¹⁸F]FDG PET/CT imaging were performed on RA (<i>n</i> = 6) and control (<i>n</i> = 6) mice. The Logan kinetic model with a graphical arterial input function analysis was used to quantitatively evaluate the in vivo expression of S1PR1. Histological and immunofluorescence (IF) staining were performed postimaging. The relationship between fibroblast-like synoviocyte (FLS) expression and [¹⁸F]TZ4877 uptake was also analyzed. [¹⁸F]TZ4877 uptake was significantly higher in CIA mice than in controls and positively correlated with arthritis scores (<i>r</i> = 0.876, <i>p</i> < 0.001). The specific binding potential (BP_ND) values of [¹⁸F]TZ4877 in the hindfoot joints of the RA group (1.33 ± 0.23) were greater than those in the control group (0.14 ± 0.04). In contrast, there was no significant difference in the [¹⁸F]FDG uptake between the two groups. IF staining demonstrated the colocalization of S1PR1 with FLS in the hindfoot joints of CIA mice. Quantitative analysis indicated that in areas with greater numbers of FLSs, the expression of S1PR1 was correspondingly increased. In PET/CT imaging of RA, [¹⁸F]TZ4877 can be used to detect the expression of S1PR1 effectively in CIA mouse models. The radiotracer holds promise as a noninvasive tool for the quantitative diagnosis of RA.