A Randomized Trial on the Optimization of 18F-FDG Myocardial Uptake Suppression: Implications for Vulnerable Coronary Plaque Imaging

18F-FDG PET/CT can be used to detect arterial atherosclerotic plaque inflammation. However, avid myocardial glucose uptake may preclude its use for visualizing coronary plaques. Fatty acid loading or calcium channel blockers could decrease myocardial 18F-FDG uptake, thus assisting coronary plaque inflammation identification. The present prospective randomized trial compared the efficacies of different interventions for suppressing myocardial 18F-FDG uptake. We also investigated whether circulating free fatty acid (cFFA) levels predicted the magnitude of myocardial 18F-FDG uptake. Methods: Thirty-six volunteers ate a high-fat low-carbohydrate meal, followed by a 12-h fasting period. They were then randomized to 1 of 4 intervention groups. Group 1 received no additional preparation and served as a reference. Groups 2 and 3, respectively, received a commercial high-fat solution containing 43.8 g of lipids or 50 mL of olive oil 1 h before 18F-FDG injection to evaluate the impact of fatty acid loading on myocardial 18F-FDG uptake. Group 4 received verapamil to evaluate the effect of calcium channel blockers. Cardiac PET/CT was performed after administration of 370 MBq of 18F-FDG. Myocardial uptake suppression was assessed using a qualitative visual scale and by measuring the myocardial maximum standardized uptake value (SUVmax). Insulin, glucose, and cFFA were serially measured. Results: The qualitative visual scale showed good myocardial 18F-FDG uptake suppression in 8 of 9, 5 of 9, 4 of 9, and 8 of 9 subjects of groups 1, 2, 3, and 4, respectively (P = 0.09). SUVmax did not significantly differ between groups (P = 0.17). Interestingly, cFFA levels were higher in volunteers with good suppression (0.80 ± 0.31 mmol/L) than in those with poor suppression (0.53 ± 0.15 mmol/L; P = 0.011). We found an inverse correlation between cFFA level (measured at 18F-FDG injection) and the SUVmax (R = 0.61). Receiver-operating-characteristic curve analysis identified 0.65 mmol/L cFFA as the best cutoff value to predict adequate 18F-FDG uptake suppression (positive predictive value, 89%). Conclusion: A high-fat low-carbohydrate meal followed by a 12-h fasting period effectively suppressed myocardial 18F-FDG uptake in most subjects. Neither complementary fatty acid loading nor verapamil administered 1 h before 18F-FDG injection conferred any additional benefit. Myocardial 18F-FDG uptake was inversely correlated with cFFA level, representing an interesting way to predict myocardial 18F-FDG uptake suppression.

[1]  M. Dweck,et al.  18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial , 2014, The Lancet.

[2]  Y. Momiyama,et al.  Inflammation, Atherosclerosis and Coronary Artery Disease , 2014, Clinical Medicine Insights. Cardiology.

[3]  T. Brady,et al.  Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. , 2013, JACC. Cardiovascular imaging.

[4]  T. Imaizumi,et al.  Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging. , 2013, JACC. Cardiovascular imaging.

[5]  Ronald Boellaard,et al.  EARL FDG-PET/CT accreditation program: Feasibility, overview and results of first 55 successfully accredited sites , 2013 .

[6]  A. Davies,et al.  Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography. , 2012, European heart journal.

[7]  R. Coulden,et al.  Suppression of myocardial 18F-FDG uptake with a preparatory “Atkins-style” low-carbohydrate diet , 2012, European Radiology.

[8]  D. Dey,et al.  Coronary Arterial 18F-FDG Uptake by Fusion of PET and Coronary CT Angiography at Sites of Percutaneous Stenting for Acute Myocardial Infarction and Stable Coronary Artery Disease , 2012, The Journal of Nuclear Medicine.

[9]  P. Libby,et al.  Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography. , 2011, Journal of the American College of Cardiology.

[10]  J. Pavía,et al.  Reduced myocardial 18F-FDG uptake after calcium channel blocker administration. Initial observation for a potential new method to improve plaque detection , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[11]  Agnes Pasquet,et al.  Imaging the vulnerable plaque. , 2011, Journal of the American College of Cardiology.

[12]  V. Fuster,et al.  Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time? , 2010, Journal of the American College of Cardiology.

[13]  Ahmed Tawakol,et al.  Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. , 2010, JACC. Cardiovascular imaging.

[14]  D. Berman,et al.  Impact of carbohydrate restriction with and without fatty acid loading on myocardial 18F-FDG uptake during PET: A randomized controlled trial , 2009, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[15]  M. Reiser,et al.  18F-FDG PET/CT Identifies Patients at Risk for Future Vascular Events in an Otherwise Asymptomatic Cohort with Neoplastic Disease , 2009, Journal of Nuclear Medicine.

[16]  B. Hutton,et al.  Vascular Inflammation Imaging with 18F-FDG PET/CT: When to Image? , 2009, Journal of Nuclear Medicine.

[17]  J. Wykrzykowska,et al.  Imaging of Inflamed and Vulnerable Plaque in Coronary Arteries with 18F-FDG PET/CT in Patients with Suppression of Myocardial Uptake Using a Low-Carbohydrate, High-Fat Preparation , 2009, Journal of Nuclear Medicine.

[18]  G. Kolodny,et al.  Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet. , 2008, AJR. American journal of roentgenology.

[19]  Icrp Main Text , 2008, Annals of the ICRP.

[20]  Masatoshi Ishibashi,et al.  The prevalence of inflammation in carotid atherosclerosis: analysis with fluorodeoxyglucose-positron emission tomography. , 2007, European heart journal.

[21]  Ahmed Tawakol,et al.  In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. , 2006, Journal of the American College of Cardiology.

[22]  M. Nishimura,et al.  Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis. , 2005, European heart journal.

[23]  H. Watabe,et al.  (18)F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  O. Prante,et al.  Uptake of [18F]fluorodeoxyglucose in human monocyte-macrophages in vitro , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[25]  C. Dence,et al.  Impact of aging on substrate metabolism by the human heart. , 2003, Journal of the American College of Cardiology.

[26]  J. Vanoverschelde,et al.  Glucose for the heart. , 1999, Circulation.

[27]  S. Moore,et al.  Pathogenesis of atherosclerosis. , 1985, Metabolism: clinical and experimental.

[28]  Mark D. Huffman,et al.  Heart disease and stroke statistics--2013 update: a report from the American Heart Association. , 2013, Circulation.

[29]  J. D. Harrison,et al.  Radiation Dose to Patients from Radiopharmaceuticals , 1988 .