Original Research
In Vivo Coronary 18F-Sodium Fluoride Activity: Correlations With Coronary Plaque Histological Vulnerability and Physiological Environment

https://doi.org/10.1016/j.jcmg.2022.03.018Get rights and content

Abstract

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.

Section snippets

Study population

There were 569 coronary artery disease (CAD) patients who were scheduled for coronary artery bypass grafting (CABG)15 in Beijing Anzhen hospital between February 2018 and October 2021. Inclusion in this study required that patients were scheduled for CABG with adjunctive coronary endarterectomy (CE). Patients were excluded from this study for the following reasons: 1) a recent myocardial infarction (<4 weeks); 2) history of malignancy, acute or chronic inflammatory, and autoimmune disease; 3)

Patient characteristics

We included 55 specimens from 42 patients. Patients were predominantly elder men with multiple cardiovascular risk factors (Table 1). In total 52 specimens from 39 patients were used for pathological analysis. Three specimens from 3 patients were used for ex vivo 18F-NaF micro-PET/CT scan and radioactivity measurement. No significant difference was observed in clinical characteristics between patients with higher TBR and lower TBR (Supplemental Table 3).

Reproducibility assessment

For interobserver variability,

Discussion

In this study, we found the specificity and sensitivity of coronary 18F-NaF activity in detecting high-risk plaques and coronary 18F-NaF activity was significantly correlated with ex-vivo plaque vulnerable features of histology. In addition, the chemisorption of 18F-NaF within the plaque was related to intraplaque inflammation. In vivo coronary 18F-NaF activity was associated with high-risk features on coronary CTA. Thus, although most of the coronary atherosclerotic plaque ruptures do not lead

Conclusions

In vivo coronary 18F-NaF activity was significantly associated with ex-vivo coronary plaques histological vulnerability. Coronary 18F-NaF activity potentially provided discriminatory value for high-risk plaque. The vascular 18F-NaF activity was associated with the physiological environment of inflammation. Further studies with clinical outcomes are warranted to determine the prognostic significance of the coronary 18F-NaF activity.

COMPETENCY IN MEDICAL KNOWLEDGE: As a promising imaging modality

Funding Support and Author Disclosures

This study was funded by the Key Medical Specialty Program of Sailing Plans organized by Beijing Municipal Administration of Hospitals (grant numbers: ZYLX202110), the National Natural Science Foundation of China (grant numbers: 81871377, 81571717), and the Research on Clinical Characteristics of Capital (grant number: Z181100001718071). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Acknowledgments

The authors express their gratitude to Drs Lei Xu, Wei Yu, Rui Wang, and Zhen Zhou, Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, for their advice on improving the manuscript.

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  • The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

    Drs Wen and Gao contributed equally to this work.

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