Huang Danxuan, Ye Peizhen, Hou Yuyi, Wu Sirui, Zhong Shuping, Jin Hongjun
Department of Rheumatology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong 519000, China.
Mol Pharm. 2025 Sep 9. doi: 10.1021/acs.molpharmaceut.5c01041.
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 [F]TZ4877 with PET/CT to assess synovial inflammation in a collagen-induced arthritis (CIA) mouse model. [F]TZ4877 and [F]FDG PET/CT imaging were performed on RA ( = 6) and control ( = 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 [F]TZ4877 uptake was also analyzed. [F]TZ4877 uptake was significantly higher in CIA mice than in controls and positively correlated with arthritis scores ( = 0.876, < 0.001). The specific binding potential (BP) values of [F]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 [F]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, [F]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.
类风湿性关节炎（RA）是一种以关节炎症为特征的慢性自身免疫性疾病。本研究旨在使用正电子发射断层扫描/计算机断层扫描（PET/CT）的鞘氨醇-1-磷酸受体1（S1PR1）靶向示踪剂[F]TZ4877，评估胶原诱导性关节炎（CIA）小鼠模型中的滑膜炎症。对RA小鼠（n = 6）和对照小鼠（n = 6）进行了[F]TZ4877和[F]氟代脱氧葡萄糖（FDG）PET/CT成像。采用带有图形化动脉输入函数分析的洛根动力学模型，定量评估S1PR1在体内的表达。成像后进行组织学和免疫荧光（IF）染色。还分析了成纤维细胞样滑膜细胞（FLS）表达与[F]TZ4877摄取之间的关系。CIA小鼠中[F]TZ4877的摄取显著高于对照组，且与关节炎评分呈正相关（r = 0.876，P < 0.001）。RA组后足关节中[F]TZ4877的特异性结合潜能（BP）值（1.33±0.23）大于对照组（0.14±0.04）。相比之下，两组之间的[F]FDG摄取无显著差异。IF染色显示CIA小鼠后足关节中S1PR1与FLS共定位。定量分析表明，在FLS数量较多的区域，S1PR1的表达相应增加。在RA的PET/CT成像中，[F]TZ4877可有效检测CIA小鼠模型中S1PR1的表达。该放射性示踪剂有望成为RA定量诊断的无创工具。
