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应用近红外荧光光学成像技术,使用不同分子量的半花菁染料探针评估大鼠抗原诱导的关节炎及其在糖皮质激素治疗中的抑制作用。

Assessment of rat antigen-induced arthritis and its suppression during glucocorticoid therapy by use of hemicyanine dye probes with different molecular weight in near-infrared fluorescence optical imaging.

机构信息

Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.

出版信息

Invest Radiol. 2013 Oct;48(10):729-37. doi: 10.1097/RLI.0b013e3182954046.

DOI:10.1097/RLI.0b013e3182954046
PMID:23835596
Abstract

PURPOSE

Arthritic joints are ideal disease entities to be assessed via optical imaging. Here, we investigated the selective accumulation behavior of two differently sized hemicyanine optical probes in arthritic joints and its modification during glucocorticoid therapy in the course of inflammation.

MATERIALS AND METHODS

The well-standardized preclinical antigen-induced arthritis (AIA) model in rats was used. The animals were divided into 3 groups: arthritic, arthritic and dexamethasone-treated, and immunized only. After intravenous coinjection of DY-752 (size, 800 Da) and DY-682-(rat) IgG (size, 150 kDa) probes, spectrally unmixed near-infrared fluorescence images were acquired and analyzed semiquantitatively. Probe organ distribution, joint swelling, blood cell counts, joint vessel density, and histological scoring of arthritis were determined.

RESULTS

The local joint accumulation kinetics of the DY-752 probe differed from the DY-682-IgG one. In the course of AIA, probe signaling in arthritic joints was similar between each other. Joint swelling and histological scoring were in accordance with signaling. Dexamethasone treatment of rats with AIA significantly reduced both the near-infrared fluorescence signals and severity of arthritis but did not change the joint vascular density or the uptake of the probes by phagocytes. A differential biodistribution of both probes was encountered, but such an accumulation was prevented by dexamethasone treatment.

CONCLUSIONS

Near-infrared fluorescence signaling in the course of AIA closely reflects the pathophysiological events of the arthritic joint and the effects of therapy independently of the molecular size of the probe. The results show the suitability of our hemicyanine probes for imaging of arthritis.

摘要

目的

关节炎关节是通过光学成像进行评估的理想疾病实体。在这里,我们研究了两种不同大小的半花青光学探针在关节炎关节中的选择性积累行为及其在炎症过程中糖皮质激素治疗期间的变化。

材料和方法

使用标准化的大鼠抗原诱导关节炎(AIA)模型。将动物分为 3 组:关节炎组、关节炎和地塞米松治疗组、仅免疫组。在静脉注射 DY-752(大小 800 Da)和 DY-682-(大鼠)IgG(大小 150 kDa)探针后,采集并半定量分析光谱未混合的近红外荧光图像。确定探针器官分布、关节肿胀、血细胞计数、关节血管密度和关节炎组织学评分。

结果

DY-752 探针的局部关节积累动力学与 DY-682-IgG 探针不同。在 AIA 过程中,关节炎关节中探针信号彼此相似。关节肿胀和组织学评分与信号一致。用 AIA 治疗大鼠的地塞米松治疗显著降低了近红外荧光信号和关节炎的严重程度,但未改变关节血管密度或吞噬细胞对探针的摄取。遇到了两种探针的差异生物分布,但地塞米松治疗可预防这种积累。

结论

AIA 过程中的近红外荧光信号紧密反映了关节炎关节的病理生理事件以及治疗的效果,而与探针的分子大小无关。结果表明我们的半花青探针适用于关节炎成像。

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