Background

¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET)/computed tomography (CT) is a promising new approach for assessing microcalcification in vascular plaque.

Objectives

This prospective study aimed to evaluate the associations between in vivo coronary ¹⁸F-NaF PET/CT activity and ex vivo histological characteristics, to determine whether coronary ¹⁸F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of ¹⁸F-NaF adsorption to vascular microcalcification.

Methods

Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and ¹⁸F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary ¹⁸F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor-α, interleukin-1β), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High- and low- to medium-risk plaques were defined by standard pathological classification.

Results

A total of 55 specimens were obtained from 42 CAD patients. Coronary ¹⁸F-NaF activity of high-risk specimens was significantly higher than low- to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary ¹⁸F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC: 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histologically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor-α expression, and interleukin-1β expression correlated with coronary ¹⁸F-NaF activity (all P < 0.05). No significant association between coronary ¹⁸F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05).

Conclusions

Coronary ¹⁸F-NaF activity was associated with histological vulnerability, CD68 expression, inflammatory cytokines expression, but not with osteogenic differentiation cytokines expression. ¹⁸F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients.

中文翻译：

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体内冠状动脉 18F-氟化钠活性

背景

¹⁸ F-氟化钠 ( ¹⁸ F-NaF) 正电子发射断层扫描 (PET)/计算机断层扫描 (CT) 是一种很有前途的评估血管斑块微钙化的新方法。

目标

这项前瞻性研究旨在评估体内冠状动脉¹⁸ F-NaF PET/CT 活性与离体组织学特征之间的关联，以确定冠状动脉¹⁸ F-NaF 活性是否是斑块病理易损性的新型生物标志物，并探索潜在的生理学特征¹⁸ F-NaF对血管微钙化的吸附环境。

方法

冠状动脉疾病 (CAD) 患者接受了冠状动脉计算机断层扫描血管造影 (CTA) 和¹⁸ F-NaF PET/CT。在冠状动脉内膜切除术 (CE) 标本中评估组织学脆弱性和免疫组织化学特征，这些标本来自接受冠状动脉旁路移植术和辅助 CE 的患者。体内冠状动脉¹⁸ F-NaF 活性与冠状动脉 CTA 不良斑块特征和体外 CE 标本形态特征、CD68 表达、炎性细胞因子表达（肿瘤坏死因子-α、白细胞介素-1β）、成骨分化细胞因子表达（骨桥蛋白）之间的相关性, runt-related transcription factor 2, osteocalcin) 进行了评估。高风险和低风险至中风险斑块由标准病理分类定义。

结果

从 42 名 CAD 患者中获得了总共 55 个标本。高风险标本的冠状动脉¹⁸ F-NaF 活性显着高于中低风险标本（中位数 [25-75%]：1.88 [1.41-2.54] 对 1.12 [0.91-1.54]；P < 0.001 ）。冠状动脉¹⁸ F-NaF 活性在识别高风险斑块方面表现出很高的鉴别准确性 (AUC：0.80)。冠状动脉 CTA 不良斑块特征（阳性重构、低衰减斑块、重构指数）、组织学易损特征（大坏死核、薄纤维帽、微钙化）、CD68 表达、肿瘤坏死因子-α 表达和白介素-1β 表达相关具有冠状动脉¹⁸ F-NaF 活性（所有P <0.05）。未发现冠状动脉¹⁸ F-NaF 活性与成骨分化细胞因子之间存在显着关联（所有P > 0.05）。

结论

冠状动脉¹⁸ F-NaF 活性与组织学易损性、CD68 表达、炎性细胞因子表达相关，但与成骨分化细胞因子表达无关。¹⁸ F-NaF PET/CT 成像可为检测高危冠状动脉斑块提供有力工具，并可改善 CAD 患者的风险分层。