Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology

J Am Coll Cardiol. 2012 Apr 24;59(17):1539-48. doi: 10.1016/j.jacc.2011.12.037.

Abstract

Objectives: 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).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aorta, Thoracic / diagnostic imaging
  • Aorta, Thoracic / pathology
  • Biomarkers / analysis
  • Coronary Angiography / methods
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / pathology
  • Female
  • Fluorine Radioisotopes / pharmacokinetics*
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Humans
  • Male
  • Middle Aged
  • Observer Variation
  • Positron-Emission Tomography*
  • Prospective Studies
  • Reproducibility of Results
  • Risk Assessment
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Sodium Fluoride / pharmacokinetics*
  • Tomography, X-Ray Computed

Substances

  • Biomarkers
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Sodium Fluoride

Associated data

  • ClinicalTrials.gov/NCT01358513