The development and optimization of therapies for rheumatoid arthritis (RA) is currently hindered by a lack of methods for early non-invasive monitoring of treatment response. Annexin A2, an inflammation-associated protein whose presence and phosphorylation levels are upregulated in RA, represents a potential molecular target for tracking RA treatment response. LS301, a near-infrared dye-peptide conjugate that selectively targets tyrosine 23-phosphorylated annexin A2 (pANXA2), was evaluated for its utility in monitoring disease progression, remission, and early response to drug treatment in mouse models of RA by fluorescence imaging. The intraarticular distribution and localization of LS301 relative to pANXA2 was determined by histological and immunohistochemical methods. In mouse models of spontaneous and serum transfer-induced inflammatory arthritis, intravenously administered LS301 showed selective accumulation in regions of joint pathology including paws, ankles, and knees with positive correlation between fluorescent signal and disease severity by clinical scoring. Whole-body near-infrared imaging with LS301 allowed tracking of spontaneous disease remission and the therapeutic response after dexamethasone treatment. Histological analysis showed preferential accumulation of LS301 within the chondrocytes and articular cartilage in arthritic mice, and colocalization was observed between LS301 and pANXA2 in the joint tissue. We demonstrate that fluorescence imaging with LS301 can be used to monitor the progression, remission, and early response to drug treatment in mouse models of RA. Given the ease of detecting LS301 with portable optical imaging devices, the agent may become a useful early treatment response reporter for arthritis diagnosis and drug evaluation.

中文翻译：

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通过靶向软骨细胞中的酪氨酸磷酸化膜联蛋白 A2 无创监测关节炎治疗反应

目前，由于缺乏早期无创监测治疗反应的方法，类风湿性关节炎 (RA) 疗法的开发和优化受到阻碍。膜联蛋白 A2 是一种炎症相关蛋白，其存在和磷酸化水平在 RA 中上调，代表了跟踪 RA 治疗反应的潜在分子靶点。LS301 是一种近红外染料-肽结合物，可选择性靶向酪氨酸 23-磷酸化膜联蛋白 A2 (pANXA2)，通过荧光成像评估其在 RA 小鼠模型中监测疾病进展、缓解和药物治疗早期反应的效用。LS301 相对于 pANXA2 的关节内分布和定位通过组织学和免疫组织化学方法确定。在自发性和血清转移诱导的炎症性关节炎小鼠模型中，静脉注射 LS301 显示在关节病理学区域（包括爪子、脚踝和膝盖）的选择性积累，荧光信号与临床评分的疾病严重程度呈正相关。使用 LS301 的全身近红外成像可以跟踪自发疾病缓解和地塞米松治疗后的治疗反应。组织学分析显示 LS301 在关节炎小鼠的软骨细胞和关节软骨内优先积累，并且在关节组织中观察到 LS301 和 pANXA2 之间存在共定位。我们证明，使用 LS301 的荧光成像可用于监测 RA 小鼠模型的进展、缓解和对药物治疗的早期反应。