In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis.

IF 2.2 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Molecular Imaging Pub Date : 2017-01-01 DOI:10.1177/1536012117712638

Benjamin L Franc, Sam Goth, John MacKenzie, Xiaojuan Li, Joseph Blecha, Tina Lam, Salma Jivan, Randall A Hawkins, Henry VanBrocklin

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引用次数: 25

Abstract

Background: Evolving immune-mediated therapeutic strategies for rheumatoid arthritis (RA) may benefit from an improved understanding of the complex role that T-cell activation plays in RA. This study assessed the potential of fluorine-18-labeled 9-β-d-arabinofuranosylguanine ([¹⁸F]F-AraG) positron emission tomography (PET) imaging to report immune activation in vivo in an adjuvant-induced arthritis (AIA) small animal model.

Methods: Using positron emission tomography-computed tomography imaging, uptake of [¹⁸F]F-AraG in the paws of mice affected by arthritis at 6 (acute) and 20 (chronic) days following AIA induction in a single paw was assessed and compared to uptake in contralateral control paws. Fractions of T cells and B cells demonstrating markers of activation at the 2 time points were determined by flow cytometry.

Results: Differential uptake of [¹⁸F]F-AraG was demonstrated on imaging of the affected joint when compared to control at both acute and chronic time points with corresponding changes in markers of T-cell activation observed on flow cytometry.

Conclusion: [¹⁸F]F-AraG may serve as an imaging biomarker of T-cell activation in inflammatory arthritis. Further development of this technique is warranted and could offer a tool to explore the temporal link between activated T cells and RA as well as to monitor immune-mediated therapies for RA in clinical trials.

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炎性关节炎小动物模型激活免疫环境的体内PET成像。

背景:对t细胞活化在类风湿关节炎(RA)中所起的复杂作用的更好理解可能会使免疫介导的类风湿性关节炎(RA)治疗策略的发展受益。本研究评估了氟-18标记的9-β-d-阿拉伯糖脲基鸟嘌呤([18F]F-AraG)正电子发射断层扫描(PET)成像在佐剂性关节炎(AIA)小动物模型中报告体内免疫激活的潜力。方法:采用正电子发射断层扫描-计算机断层成像技术，评估AIA诱导后6天(急性)和20天(慢性)单爪关节炎小鼠爪子中[18F]F-AraG的摄取情况，并与对侧对照爪子的摄取情况进行比较。流式细胞术检测在2个时间点显示活化标记的T细胞和B细胞的组分。结果:在急性和慢性时间点，与对照组相比，受影响关节的影像学显示[18F]F-AraG的摄取差异，流式细胞术观察到t细胞活化标志物的相应变化。结论:[18F]F-AraG可能是炎症性关节炎中t细胞活化的影像学生物标志物。这项技术的进一步发展是必要的，可以为探索活化T细胞和RA之间的时间联系以及在临床试验中监测RA的免疫介导疗法提供工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology

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3.60%

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期刊介绍： Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.