title: Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology.
abstract: OBJECTIVE
  With combined positron emission tomography and computed tomography (CT), we investigated coronary arterial uptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively.
  
  
  BACKGROUND
  The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation.
  
  
  METHODS
  We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score >0).
  
  
  RESULTS
  Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p < 0.001), although 40% of those with scores >1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498).
  
  
  CONCLUSIONS
  18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).
authors.affiliation: Centre for Cardiovascular Sciences, University of Edinburgh, United Kingdom. MDweck@staffmail.ed.ac.uk
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
authors.forename: Marcus W L
authors.initials: MW
authors.lastname: Chow
authors.forename: Nikhil V
authors.initials: NV
authors.lastname: Joshi
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Williams
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jones
authors.forename: Alison M
authors.initials: AM
authors.lastname: Fletcher
authors.forename: Hamish
authors.initials: H
authors.lastname: Richardson
authors.forename: Audrey
authors.initials: A
authors.lastname: White
authors.forename: Graham
authors.initials: G
authors.lastname: McKillop
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Boon
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D000368:Aged; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012969:Sodium Fluoride / Q000493:pharmacokinetics*; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D012969:Sodium Fluoride