Division of Rheumatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
J Bone Miner Res. 2019 Sep;34(9):1632-1645. doi: 10.1002/jbmr.3748. Epub 2019 Jul 30.
In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([ F]FDG) and [ F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [ F]FDG, for detecting inflammatory processes, or [ F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV ) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [ F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [ F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [ F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
在类风湿关节炎（RA）中，导致骨和软骨损伤的慢性关节炎症是功能障碍的主要原因。虽然疾病修饰抗风湿疗法可以成功减少滑膜炎和阻止关节损伤，但治疗干预后的骨修复仅很少有报道。本研究的目的是使用氟脱氧葡萄糖（[F]FDG）和[F]氟化物μPET/CT 成像来监测系统性炎症和破坏性骨重塑过程以及在慢性炎症性、侵蚀性多关节炎的既定小鼠模型中潜在的骨修复。因此，用人肿瘤坏死因子转基因（hTNFtg）小鼠进行英夫利昔单抗（一种抗 TNF 抗体）治疗 4 周。在治疗前后，小鼠接受[F]FDG（用于检测炎症过程）或[F]氟化物（用于监测骨重塑过程）进行 PET 扫描，然后进行 CT 扫描。分析了各种关节的标准化摄取值（SUV），并评估了关节炎、关节损伤和修复的组织病理学迹象。纵向 PET/CT 扫描显示受影响关节中的[F]FDG SUV 显著降低，表明 TNF 阻断导致炎症过程完全缓解。相比之下，[F]氟化物 SUV 无法区分 hTNFtg 小鼠中不同严重程度的骨损伤。重复的体内 CT 图像证明了抗 TNF 治疗后先前存在的骨侵蚀的结构逆转。因此，组织学分析显示滑膜炎症完全消退，骨侵蚀部位的骨愈合。我们得出结论，体内多模态[F]FDGμPET/CT 成像可定量和监测炎症介导的骨损伤，不仅揭示了滑膜炎的逆转，而且在实验性关节炎中还揭示了 TNF 阻断后的骨修复。©2019 作者。骨与矿物研究杂志由 Wiley 期刊出版公司出版。
