Thresholds for Arterial Wall In fl ammation Quanti fi ed by 18 F-FDG PET Imaging Implications for Vascular Interventional Studies

Fro Ep Am D Me 7 g (no Re ha Ma OBJECTIVES This study assessed 5 frequently applied arterial fluorodeoxyglucose (F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies. BACKGROUND F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available. METHODS F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results. RESULTS All F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta. CONCLUSIONS We report thresholds for physiological F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006) (J Am Coll Cardiol Img 2016;9:1198–207) © 2016 by the American College of Cardiology Foundation. Published by Elsevier. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). m the Department of Vascular Medicine, Academic Medical Centre, Amsterdam, the Netherlands; Department of Clinical idemiology, Academic Medical Center, Amsterdam, the Netherlands; Department of Radiology, Academic Medical Center, sterdam, the Netherlands; Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, the Netherlands; epartment of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands; and the Division of Cardiovascular dicine, University of Cambridge, Cambridge, United Kingdom. This work was supported by a European Framework Program rant (ESS: FP7-Health 309820: Nano-Athero). Dr. Stroes has received lecture fees from Merck, Novartis, ISIS, and Amgen ne of which are related to the contents of this paper). Dr. Rudd is partly supported by the National Institute for Health search Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust. All other authors ve reported that they have no relationships relevant to the contents of this paper to disclose. nuscript received August 18, 2015; revised manuscript received March 22, 2016, accepted April 21, 2016. AB BR E V I A T I O N S