18F-Sodium Fluoride PET/CT in Assessing Valvular Heart and Atherosclerotic Diseases.

Aortic valve stenosis is the most common valvular disease in Western countries, while atherosclerotic cardiovascular disease is the foremost cause of death and disability worldwide. Valve degeneration and atherosclerosis are mediated by inflammation and calcification and inevitably progress over time. Computed tomography can visualise the later stages of macroscopic calcification but fails to assess the early stages of microcalcification and cannot differentiate active from burnt out disease states. Molecular imaging has the ability to provide complementary information related to disease activity, which may allow us to detect disease early, to predict disease progression and to monitor preventive or therapeutic strategies for in both aortic stenosis and atherosclerosis. PET/CT is a non-invasive imaging technique that enables visualization of ongoing molecular processes within small structures, such as the coronary arteries or heart valves. 18F-sodium fluoride (18F-NaF) binds hydroxyapatite deposits in the extracellular matrix, with preferential binding to newly developing deposits of microcalcification, which provides an assessment of calcification activity. In recent years, 18F-NaF has attracted the attention of many research groups and has been evaluated in several pathological cardiovascular processes. Histologic validation of the 18F-NaF PET signal in valvular disease and atherosclerosis has been reported in multiple independent studies. The selective high-affinity binding of 18F-NaF to microscopic calcified deposits (beyond the resolution of µCT) has been demonstrated ex vivo, as well as its ability to distinguish between areas of macro- and active microcalcification. In addition, prospective clinical studies have shown that baseline 18F-NaF uptake in patients with aortic stenosis and mitral annular calcification is correlated with subsequent calcium deposition and valvular dysfunction after a follow-up period of 2 years. In patients with surgical bioprosthetic aortic valves but without morphological criteria for prosthetic degeneration, increased 18F-NaF uptake at baseline was associated with subsequent bioprosthetic degeneration over time. Similar data were obtained in a cohort of patients with transcatheter aortic valve implantation. Furthermore, several studies have confirmed the association of coronary 18F-NaF uptake with adverse atherosclerotic plaque features, active disease and future disease progression. 18F-NaF uptake is also associated with future fatal or nonfatal myocardial infarction in patients with established coronary artery disease. The link between 18F-NaF uptake and active atherosclerotic disease has not only been demonstrated in the coronary arteries, but also in peripheral arterial disease, abdominal aortic aneurysms and carotid atherosclerosis. It can be assumed that 18F-NaF PET/CT will strengthen the diagnostic toolbox of practitioners in the coming years. Indeed, there is a strong medical need to diagnose degenerative valvular disease and to detect active atherosclerotic disease states. Finally, the use of 18F-NaF as a biomarker to monitor the efficacy of drug therapies in preventing these pathological processes is attractive. In this review, we consider the role of 18F-NaF PET/CT imaging in cardiac valvular diseases and atherosclerosis.

A randomized trial on the optimization of 18F-FDG myocardial uptake suppression: implications for vulnerable coronary plaque imaging.

UNLABELLED: (18)F-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 (18)F-FDG uptake, thus assisting coronary plaque inflammation identification. The present prospective randomized trial compared the efficacies of different interventions for suppressing myocardial (18)F-FDG uptake. We also investigated whether circulating free fatty acid (cFFA) levels predicted the magnitude of myocardial (18)F-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 (18)F-FDG injection to evaluate the impact of fatty acid loading on myocardial (18)F-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 (18)F-FDG. Myocardial uptake suppression was assessed using a qualitative visual scale and by measuring the myocardial maximum standardized uptake value (SUV(max)). Insulin, glucose, and cFFA were serially measured. RESULTS: The qualitative visual scale showed good myocardial (18)F-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). SUV(max) 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 (18)F-FDG injection) and the SUV(max) (R = 0.61). Receiver-operating-characteristic curve analysis identified 0.65 mmol/L cFFA as the best cutoff value to predict adequate (18)F-FDG uptake suppression (positive predictive value, 89%). CONCLUSION: A high-fat low-carbohydrate meal followed by a 12-h fasting period effectively suppressed myocardial (18)F-FDG uptake in most subjects. Neither complementary fatty acid loading nor verapamil administered 1 h before (18)F-FDG injection conferred any additional benefit. Myocardial (18)F-FDG uptake was inversely correlated with cFFA level, representing an interesting way to predict myocardial (18)F-FDG uptake suppression.