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成纤维细胞激活蛋白抑制剂正电子发射断层扫描在大动脉炎中的应用:炎症活动期和缓解期的成纤维细胞病理学。

Fibroblast activation protein inhibitor-positron emission tomography in aortitis: fibroblast pathology in active inflammation and remission.

机构信息

Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany.

Department of Nuclear Medicine, Mainz University Hospital, Mainz, Germany.

出版信息

Rheumatology (Oxford). 2024 Sep 1;63(9):2473-2483. doi: 10.1093/rheumatology/keae225.

DOI:10.1093/rheumatology/keae225
PMID:38648749
Abstract

OBJECTIVES

Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis.

METHODS

Eight LVV patients with aortitis and eight age- and gender-matched controls were included. The distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication.

RESULTS

Three aortitis patients were clinically active and five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found. In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed.

CONCLUSIONS

This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV.

摘要

目的

表观遗传修饰的成纤维细胞有助于炎症性疾病的慢性化。大动脉血管炎(LVV)反复发作的原因仍不清楚,包括成纤维细胞的作用,部分原因是难以获得受累组织的活检。68Ga FAPI-46(FAPI)-PET/CT 可在体内检测到激活的成纤维细胞。在这项探索性的初步研究中,我们使用 FAPI-PET/CT 检测了伴有主动脉炎的 LVV 中血管壁中成纤维细胞的激活。

方法

纳入 8 例伴有主动脉炎的 LVV 患者和 8 例年龄和性别匹配的对照者。评估 FAPI 摄取在主动脉和大血管中的分布。比较 FAPI 摄取与 MRI 炎症活动评分。将影像学结果与临床参数(如血清炎症标志物、缓解时间和药物治疗)进行比较。

结果

3 例主动脉炎患者处于临床活动期,5 例处于缓解期。无论活动情况如何,主动脉炎患者的 FAPI 摄取均明显高于对照组。缓解期患者的平均缓解时间为 2.8 年(范围 1-4 年),但在血管壁中仍发现明显的 FAPI 摄取。在缓解的主动脉炎中,MRI 炎症评分接近阴性,而在 5 例患者中有 4 例观察到可识别的 FAPI 摄取。

结论

这项初步可行性研究显示 LVV 主动脉壁中存在明显的示踪剂摄取。FAPI 阳性表明临床缓解的 LVV 中持续存在成纤维细胞病理。

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