Thresholds for Arterial Wall Inflammation Quantified by ¹⁸F-FDG PET Imaging: Implications for Vascular Interventional...

This study assessed 5 frequently applied arterial ¹⁸fluorodeoxyglucose (¹⁸F-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.

¹⁸F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of ¹⁸F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available.

¹⁸F-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 ¹⁸F-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.

All ¹⁸F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological ¹⁸F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBR_max); whole artery TBR_max 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 TBR_max as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta.

We report thresholds for physiological ¹⁸F-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 ¹⁸F-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).