Elsevier

Atherosclerosis

Volume 211, Issue 1, July 2010, Pages 136-140
Atherosclerosis

What is the natural history of 18F-FDG uptake in arterial atheroma on PET/CT? Implications for imaging the vulnerable plaque

https://doi.org/10.1016/j.atherosclerosis.2010.01.012Get rights and content

Abstract

Purpose

Increased uptake of 18F-fluorodeoxyglucose (18F-FDG) in atherosclerotic plaque on Positron Emission Tomography (PET), predicts vulnerability. Recent studies have shown that the PET signal is reproducible over a 2-week period and as a result drug trials are underway. However, the natural history of these lesions is unknown. The aim of this study is determine the natural history of increased vascular wall uptake of 18F-fluorodeoxyglucose (18F-FDG).

Methods

Following institutional ethics committee approval, we retrospectively examined PET/CT images of patients from our Institution that had at least 4 examinations in the last 5 years. This represented 205 studies in total, from 50 patients (29 men, 21 women, mean age 49.4 ± 12.1 years, mean 5.1 ± 1.7 studies/patient). The mean follow-up was 27.2 ± 11.8 months. The carotids and the aorta were evaluated for increased 18F-FDG uptake with a maximum Standardized Uptake Value (SUVmax) >2.5, and >3.0, and calcification. Plots of SUVmax and Hounsfield units (HU) were made versus time.

Results

The initial prevalence of increased focal arterial 18F-FDG uptake was 17/50 patients and of arterial calcification 19/50. 132 sites of 18F-FDG uptake in total were observed longitudinally. 18F-FDG vascular uptake did not persist with time. There was no correlation between 18F-FDG uptake and HU. No calcifications developed at sites of focal increased 18F-FDG uptake.

Conclusions

Arterial lesions with increased 18F-FDG uptake represent transient phenomena. This data is important for the interpretation of findings of clinical trials using arterial 18F-FDG uptake as an imaging biomarker to monitor pharmacological intervention.

Introduction

The concept of the vulnerable arterial plaque has been increasingly recognized [1]. Successfully imaging such lesions in vivo would have a major impact on the diagnosis, prognosis and therapeutic monitoring of cardiovascular disease. There is increasing evidence that 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) has potential to non-invasively detect and quantify plaque inflammation and instability in humans [2], [3] with histological validation that there are raised inflammatory markers at these sites [2], [3]. As a continuum of this work, a study was published on near-term (2 weeks) reproducibility of the technique [4] with recommendations for clinical trials using 18F-FDG PET as a potential biomarker to monitor therapeutic intervention [5], [6]. However the pattern of uptake, changes in approximately half of patients over longer periods of time [7]. These changes in uptake must be considered when the use of 18F-FDG vascular imaging is suggested to define the efficacy of therapy [8], since the longer term natural history of arterial lesions with increased 18F-FDG uptake on PET is unknown. Indeed, it has been postulated that such uptake in these arterial lesions may be transient [9]. In order to test this clinically critical hypothesis, a longitudinal study has been recommended where it would be predicted that over time plaques that had increased 18F-FDG uptake originally would lose their avidity [9]. However to test this theory prospectively would be ethically difficult, both with respect to the required repeated exposure to ionizing radiation and withholding of treatment from symptomatic patients.

We therefore performed retrospective longitudinal 18F-FDG vascular measurements on patients to evaluate the natural history of avid arterial plaques on PET/computed tomography (CT).

Section snippets

Patients

We retrospectively examined PET/CT images from all the patients presenting to our institution in the last 4 years, who had had a minimum of 4 examinations. There were 50 patients (29 men, 21 women, mean age at presentation 49.4. ± 12.1, with an average of 5.1 ± 1.7 studies per patient). This represented 205 PET/CT studies in total. The local institutional ethics committee approved the research protocol. All the patients were referred for tumour staging, therapy monitoring or re-staging. Their

Results

A total of 205 studies were reviewed. The mean number of studies per patient was 5.1 ± 1.7. The mean time between studies was 6.5 ± 5.5 months. The mean length of follow-up was 27.2 ± 11.8 months. The clinical characteristics of the study population are presented in Table 1.

At initial presentation, there were 17/50 (34%) patients who had increased vessel wall 18F-FDG uptake and 19/50 (38%) patients who had arterial calcification. There were 5 sites where there was focal 18F-FDG uptake at sites of

Discussion

By taking multiple longitudinal SUV measurements, we have shown that areas of focal arterial 18F-FDG uptake are transient, and that (in the study time frame) there is no relationship between arterial 18F-FDG uptake and calcification. Given that there is considerable evidence that 18F-FDG is a marker for plaque instability [2], [3], [10], then these results yield insight into the natural history of these arterial lesions, which could translate into important clinical implications, since 18F-FDG

Conclusion

Using longitudinal PET/CT measurements on single patients, the natural history of focal arterial of 18F-FDG uptake has been shown to be a transient phenomenon. This data is important for the interpretation of findings from clinical trials using arterial 18F-FDG uptake as a imaging biomarker to monitor pharmacological intervention, and predicting clinical events in high-risk patients.

Conflict of interest

No author has any conflict of interest or relevant financial disclosure.

Acknowledgements

This work was undertaken at UCLH/UCL who received a proportion of funding from the UK's Department of Health's NIHR Biomedical Research Centres funding scheme.

This work was awarded the Finzi Prize by the Royal Society of Medicine, London, UK and thus received a small financial award.

The experiments herein comply with the current laws of the United Kingdom inclusive of ethics approval.

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