Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China; Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University, #6699, Qingdao Road, Jinan, 250017, China.
College of Preventive Medical Sciences (Institute of Radiation Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, China.
Mol Imaging Biol. 2023 Aug;25(4):630-637. doi: 10.1007/s11307-023-01817-6. Epub 2023 Apr 5.
Fibroblast activating protein (FAP) is highly expressed in the synovial tissues of rheumatoid arthritis (RA) patients. The aim of this study was to determine the feasibility of PET imaging with an Al[F] F-NOTA-labeled FAP inhibitor 04(F-FAPI-04) for the evaluation of arthritic progression and therapeutic response in experimental arthritis.
Fibroblast-like synoviocytes (FLSs) were obtained from patients with RA or osteoarthritis (OA), and the relationship between F-FAPI-04 uptake and the inflammatory activity of RA FLSs was investigated. Collagen-induce arthritis (CIA) mice models were established and treated with methotrexate (MTX) or etanercept (ETC). Then, PET imaging was performed 24 h following F-FAPI-04 injection. The imaging results were compared by assessing macroscopic arthritis scores and histological staining.
F-FAPI-04 uptake was obvious in RA FLSs that characterizing FAP activation. The higher the uptake of F-FAPI-04, the more severity of the inflammatory phenotype in RA FLS. Furthermore, the uptake of F-FAPI-04 in inflamed joints could be found even before the deformity of the parental joints could be observed by histological examination. Both MTX and ETC were effective in inhibiting the progression of arthritis in CIA mice was confirmed by macroscopic, histological, and radiographic pathology scores. Importantly, F-FAPI-04 uptake declined accordingly in CIA models following MTX and ETC treatment.
These findings suggest that PET imaging of F-FAPI-04 can be used to monitor treatment response in RA, and is more sensitive in disease speculation than macroscopic arthritis scoring.
成纤维细胞激活蛋白（FAP）在类风湿关节炎（RA）患者的滑膜组织中高度表达。本研究旨在确定使用 Al[F] F-NOTA 标记的 FAP 抑制剂 04（F-FAPI-04）进行 PET 成像以评估实验性关节炎中关节炎进展和治疗反应的可行性。
从 RA 或骨关节炎（OA）患者中获得成纤维样滑膜细胞（FLS），并研究 F-FAPI-04 摄取与 RA FLS 炎症活性之间的关系。建立胶原诱导性关节炎（CIA）小鼠模型，并接受甲氨蝶呤（MTX）或依那西普（ETC）治疗。然后，在注射 F-FAPI-04 后 24 小时进行 PET 成像。通过评估宏观关节炎评分和组织学染色来比较成像结果。
F-FAPI-04 在 RA FLS 中的摄取明显，其特征是 FAP 激活。F-FAPI-04 的摄取越高，RA FLS 的炎症表型越严重。此外，甚至在组织学检查发现亲本关节变形之前，就可以在发炎的关节中发现 F-FAPI-04 的摄取。通过宏观、组织学和放射病理学评分证实，MTX 和 ETC 均能有效抑制 CIA 小鼠关节炎的进展。重要的是，在 CIA 模型中，在接受 MTX 和 ETC 治疗后，F-FAPI-04 的摄取相应下降。
这些发现表明，F-FAPI-04 的 PET 成像可用于监测 RA 的治疗反应，并且在疾病推测方面比宏观关节炎评分更敏感。
