Implementing point-of-care ketone testing and a 'three zone' ketone interpretation framework to predict dietary preparation and myocardial suppression in FDG PET for cardiac inflammation

Introduction/Background Physiological myocardial FDG uptake limits the diagnostic accuracy of FDG PET for detecting cardiac inflammation. Suppressing myocardial glucose metabolism requires prolonged fasting and high-fat, low-carbohydrate diets. However, adherence varies and is difficult to verify objectively. Beta-hydroxybutyrate (BHB), the main circulating ketone, rises with fasting and reflects a shift from glucose to fatty acid metabolism. Purpose This study evaluated whether point-of-care (POC) BHB levels correlate with physiological myocardial FDG uptake, and whether it can serve as an objective marker of fasting adequacy and myocardial suppression. Methods All FDG PET scans for cardiac inflammation from 2018 to mid-2025 were reviewed for reported physiological myocardial uptake. From mid-2025, pre-scan POC BHB was measured before all cardiac inflammation and non-cardiac FDG PET scans. Because fasting before cardiac inflammation scans is more prolonged than for non-cardiac scans, comparing BHB between the two assessed whether BHB reflects fasting duration. Mean BHB levels were compared with Welch’s t-test, and ROC analysis evaluated discriminative performance and identified optimal cut-offs. Results Of 716 cardiac inflammation FDG PET scans, 631 (88.1%) reported no physiological uptake and 85 (11.9%) did. After introducing BHB testing, 162 scans were performed (47 cardiac inflammation, 115 non-cardiac). Mean BHB was higher in cardiac inflammation scans than non-cardiac scans (0.44 ± 0.32 vs. 0.27 ± 0.24 mmol/L, p < 0.01). Within cardiac inflammation scans, BHB was higher in well-suppressed studies (0.46 ± 0.33 mmol/L) than those with physiological uptake (0.24 ± 0.13 mmol/L, p ≈ 0.04). Five of 47 (10.6%) cardiac inflammation scans showed physiological uptake, with 2 out of 5 having BHB ≤0.1 mmol/L. ROC analysis (AUC 0.76) supported a ‘three-zone’ ketone-interpretation framework: BHB ≤0.1 mmol/L was associated with inadequate suppression (capturing 40% of uptake-positive scans); BHB ≥0.5 mmol/L strongly indicated adequate suppression (100% sensitivity and 100% negative predictive value for absence of physiological uptake); and 0.1–0.5 mmol/L formed a ‘grey area’ that included 50% of cardiac inflammation scans. Conclusion Pre-scan BHB provides an objective marker of fasting adequacy in cardiac inflammation FDG PET. BHB ≤0.1 mmol/L strongly suggests inadequate suppression, BHB ≥0.5 mmol/L reliably indicates adequate suppression, and 0.1–0.5 mmol/L is a clinically important ‘grey area’. Incorporating POC BHB measurement into routine practice can improve confidence in scan interpretation and diagnostic accuracy. This is the first real-world study to incorporate POC BHB testing into cardiac inflammation FDG PET, to validate its importance through comparison with non-cardiac scans, and to introduce a clinically practical ‘three-zone’ ketone interpretation framework.