Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan.
Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Maebashi, Japan.
Mod Rheumatol. 2021 Mar;31(2):350-356. doi: 10.1080/14397595.2020.1751945. Epub 2020 Apr 23.
Molecular imaging constitutes a promising technique for the early detection of rheumatoid arthritis (RA). Macrophages and hypoxia play significant roles in inflamed synovium. In the present study, we evaluated the efficacy of radiopharmaceuticals that target macrophage mannose receptors (Tc-labeled mannosylated dextran or Tc(CO)-DCM20) and hypoxia (copper(II) diacetyl-di(N-methylthiosemicarbazone) or Cu-ATSM) for the early detection of RA in collagen-induced arthritis (CIA) mice models.
CIA model was developed in DBA/1 mice, and the clinical score for arthritis was visually assessed on a regular basis. Two biodistribution studies were performed in a paired-labeled format using 2-deoxy-2-F-fluoro-D-glucose (F-FDG) as a reference: (1) Tc(CO)-DCM20 with F-FDG and (2) Cu-ATSM with F-FDG.
The accumulation levels of Tc(CO)-DCM20 and Cu-ATSM in forepaws, hindpaws, and knee joints of CIA mice were significantly higher than that of control mice. In contrast, F-FDG uptake in hindpaws and knee joints showed no significant difference between CIA and control mice. The radioactivity levels of Tc(CO)-DCM20 and Cu-ATSM were significantly correlated with the clinical scores for the paws.
These results suggest the potential usefulness of Tc(CO)-DCM20 and radiolabeled Cu-ATSM for the imaging and early detection of RA.
分子影像学是一种很有前途的技术，可用于早期检测类风湿关节炎（RA）。巨噬细胞和缺氧在发炎的滑膜中起着重要作用。在本研究中，我们评估了针对巨噬细胞甘露糖受体（Tc 标记的甘露糖化葡聚糖或 Tc(CO)-DCM20）和缺氧（铜（II）乙酰二肟二（N-甲基硫代半卡巴腙）或 Cu-ATSM）的放射性药物在胶原诱导性关节炎（CIA）小鼠模型中早期检测 RA 的功效。
在 DBA/1 小鼠中建立 CIA 模型，并定期进行关节炎临床评分的视觉评估。采用双示踪剂格式进行了两项生物分布研究，以 2-脱氧-2-F-氟-D-葡萄糖（F-FDG）作为参考：（1）Tc(CO)-DCM20 与 F-FDG 和（2）Cu-ATSM 与 F-FDG。
Tc(CO)-DCM20 和 Cu-ATSM 在 CIA 小鼠前爪、后爪和膝关节中的积聚水平明显高于对照组。相比之下，F-FDG 在 CIA 和对照组小鼠后爪和膝关节中的摄取无明显差异。Tc(CO)-DCM20 和 Cu-ATSM 的放射性水平与爪子的临床评分显著相关。
这些结果表明 Tc(CO)-DCM20 和放射性标记的 Cu-ATSM 具有用于成像和早期检测 RA 的潜在用途。
