Discrepancy between in vivo cardiac uptake of 18F-NaF, atherosclerotic plaque, and biochemical assessment of calcification

Objectives Increasingly, 18F-NaF uptake is being accepted as a reliable imaging biomarker for identification of high-risk atherosclerotic plaques and cardiac disease.However, limited data are available about the correlation between 18F-NaF uptake and histopathological findings.The aim of this study was to compare in vivo global cardiac 18F-NaF uptake and intravascular ultrasound (IVUS) measurement of plaque burden with biochemical measurement of myocardial calcification in a swine model.

Methods After 50 weeks of atherogenic diet, Ossabaw miniature swine (n=14) underwent EKG-gated 18F-NaF PET/CT scan. Regional SUVmax,SUVmean and SUVtotal (cardiac volume*SUVmean) were measured to quantify 18F-NaF uptake in the myocardium.Plaque burden in the left anterior descending (LAD) artery was determined by IVUS. Calcium deposited in the left ventricles was determined by HCl total Ca extraction assay.

Results HCl assay and IVUS measurements showed a spectrum of disease, with total Ca ranging between 834-1704 (umol/g) and LAD plaque burden varied between 19-28%. Uptake indices of 18F-NaF also showed similar spread of values for SUVmax, SUVmean and SUVtotal, which ranged between 2.45-11.25, 0.4-1.5 and 132.3-544.5, respectively. No significant correlation was noted between 18F-NaF uptake parameters and plaque burden or total myocardial Ca values.

Conclusions These data suggest that active calcification in atherosclerotic plaque or myocardium reflected by 18F-NaF imaging does not correlate with total deposited myocardial calcium, which is quantifiable by conventional imaging modalities,or plaque burden measured by IVUS.Therefore, further studies related to association of 18F-NaF PET/CT imaging as an in vivo surrogate measure of active calcification in atherosclerotic plaque and myocardium and their relevance to clinical outcomes should be explored for cardiovascular risk stratification.

Research Support Pharmavite LLC, Nestle, Kraft Foods Inc., Fonterra Co-operative Group Limited, the Dairy Research Institute, Dairy Australia, NIH HL062552, and IU Health-IU School of Medicine Strategic Research Initiative